Nutritional opticneuropathy (aka deficiency opticneuropathy) is a dysfunction of the optic nerve resulting from improper dietary content of certain nutrients essential for normal functioning of the nerve fibers. Most commonly, it results from folic acid and vitamin B complex deficiency associated with malnutrition or poor dietary habits, incorrectly applied vegetarian diet, or chronic alcohol abuse. Obese patients after bariatric surgery constitute another risk group of opticneuropathy. Nutritional opticneuropathy is characterized by painless, gradually progressing, bilateral and symmetrical decrease in visual acuity, which can be accompanied by the color vision dysfunction. Progression of the neuropathy is associated with optic nerve atrophy, manifesting as complete disc pallor. Treatment of nutritional neuropathy includes dietary supplementation, aimed at compensating for the deficient nutrients. The treatment is mostly based on folic acid, vitamin B complex, and protein replacement, as well as eliminating risk factors of neuropathy. Early treatment commencement, prior to irreversible optic nerve atrophy, is a prerequisite of effective treatment. We would like to highlight this problem by presenting the case of a young woman in whom chronic use "water-based" diet resulted in anemia and bilateral nutritional opticneuropathy. PMID:25345287

Ischemic opticneuropathy is the most frequent cause of vision loss in middle age. Clinical and laboratory research studies have begun to clarify the natural history, clinical presentation, diagnostic criteria and pathogenesis of various ischemic nerve injuries. As a result, physicians are acquiring new tools to aid in the diagnosis and potential treatment of ischemic nerve injury. The aim of this review is to examine recent data on anterior and posterior ischemic opticneuropathy and to provide a framework for physicians to manage and counsel affected individuals. PMID:18826805

Leber hereditary opticneuropathy (LHON) and autosomal dominant optic atrophy (DOA) are the two most common inherited opticneuropathies and they result in significant visual morbidity among young adults. Both disorders are the result of mitochondrial dysfunction: LHON from primary mitochondrial DNA (mtDNA) mutations affecting the respiratory chain complexes; and the majority of DOA families have mutations in the OPA1 gene, which codes for an inner mitochondrial membrane protein critical for mtDNA maintenance and oxidative phosphorylation. Additional genetic and environmental factors modulate the penetrance of LHON, and the same is likely to be the case for DOA which has a markedly variable clinical phenotype. The selective vulnerability of retinal ganglion cells (RGCs) is a key pathological feature and understanding the fundamental mechanisms that underlie RGC loss in these disorders is a prerequisite for the development of effective therapeutic strategies which are currently limited. PMID:19001017

Ischemic opticneuropathies (IONs) consist primarily of two types: anterior ischemic opticneuropathy (AION) and posterior ischemic opticneuropathy (PION). AION comprises arteritic AION (A-AION: due to giant cell arteritis) and non-arteritic AION (NA-AION: due to other causes). PION consists of arteritic PION (A-PION: due to giant cell arteritis), non-arteritic PION (NA-PION: due to other causes), and surgical PION (a complication of several systemic surgical procedures). These five types of ION are distinct clinical entities etiologically, pathogenetically, clinically and from the management point of view. In the management of AION, the first crucial step with patients aged 50 and over is to identify immediately whether it is arteritic or not because A-AION is an ophthalmic emergency and requires urgent treatment with high-dose steroid therapy to prevent any further visual loss in one or both eyes. Patients with NA-AION, when treated with systemic corticosteroid therapy within first 2 weeks of onset, had significantly better visual outcome than untreated ones. Systemic risk factors, particularly nocturnal arterial hypotension, play major roles in the development of NA-AION; management of them is essential in its prevention and management. NA-PION patients, when treated with high-dose systemic steroid therapy during the very early stages of the disease, showed significant improvement in visual acuity and visual fields, compared to untreated eyes. A-PION, like A-AION, requires urgent treatment with high-dose steroid therapy to prevent any further visual loss in one or both eyes. There is no satisfactory treatment for surgical PION, except to take prophylactic measures to prevent its development. PMID:21350282

Many systemic antimicrobials have been implicated to cause ocular adverse effects. This is especially relevant in multidrug therapy where more than one drug can cause a similar ocular adverse effect. We describe a case of progressive loss of vision associated with linezolid therapy. A 45-year-old male patient who was on treatment with multiple second-line anti-tuberculous drugs including linezolid and ethambutol for extensively drug-resistant tuberculosis (XDR-TB) presented to us with painless progressive loss of vision in both eyes. Color vision was defective and fundus examination revealed optic disc edema in both eyes. Ethambutol-induced toxic opticneuropathy was suspected and tablet ethambutol was withdrawn. Deterioration of vision occurred despite withdrawal of ethambutol. Discontinuation of linezolid resulted in marked improvement of vision. Our report emphasizes the need for monitoring of visual function in patients on long-term linezolid treatment. PMID:24088636

Many systemic antimicrobials have been implicated to cause ocular adverse effects. This is especially relevant in multidrug therapy where more than one drug can cause a similar ocular adverse effect. We describe a case of progressive loss of vision associated with linezolid therapy. A 45-year-old male patient who was on treatment with multiple second-line anti-tuberculous drugs including linezolid and ethambutol for extensively drug-resistant tuberculosis (XDR-TB) presented to us with painless progressive loss of vision in both eyes. Color vision was defective and fundus examination revealed optic disc edema in both eyes. Ethambutol-induced toxic opticneuropathy was suspected and tablet ethambutol was withdrawn. Deterioration of vision occurred despite withdrawal of ethambutol. Discontinuation of linezolid resulted in marked improvement of vision. Our report emphasizes the need for monitoring of visual function in patients on long-term linezolid treatment. PMID:24088636

Abstract A retrobulbar block is a regional anesthetic nerve block in the retrobulbar space. Opticneuropathy following retrobulbar injection is a well-recognized and rare complication of the procedure with an unknown incidence. This article reviews the relevant literature regarding vision loss following this procedure. Mechanisms of injury to the optic nerve as well as methods that can be employed to minimize the risk of opticneuropathy will be explored, including alternatives to retrobulbar anesthesia. PMID:25325871

Ischemic opticneuropathy is of two types: anterior and posterior. Non-arteritic anterior ischemic opticneuropathy (NA-AION) is the most common type of ischemic opticneuropathy. There are three major misconceptions about NA-AION: (1) that its pathogenesis is not known, (2) that NA-AION and ischemic cerebral stroke are similar in nature, pathogenetically and in management, and (3) that there is no treatment. All these misconceptions are based on lack of in-depth knowledge of the subject. They are discussed in the light of our current scientific knowledge. The pathogenesis of NA-AION is known but is highly complex. NA-AION and ischemic cerebral stroke are very different clinical entities, pathogenetically and in management. Aspirin has no beneficial effect. Corticosteroid therapy during the initial stages can be beneficial. To reduce the risk of development of NA-AION in the other eye or of further visual loss in the same eye, it is essential to reduce as many risk factors as possible. Management of arteritic anterior ischemic opticneuropathy and of posterior ischemic opticneuropathy is discussed. PMID:23821118

A 52-year-old man with chronic hepatitis C presented with painless, bilateral, simultaneous non-arteritic anterior ischemic opticneuropathy (NAION) and peripheral neuropathy. Symptoms began 19 weeks after starting peginterferon alpha-2a. The peripheral neuropathy and vision of the right eye improved, but the vision of the left eye worsened after stopping interferon. We identified 23 additional cases of NAION during interferon alpha therapy. At least 12 of these patients suffered bilateral NAION. Patients lost vision 1–40 weeks after initiating therapy. Of 21 eyes that had documented initial and follow-up acuities, 8 improved, 1 worsened, and the rest remained stable. One patient had a painful peripheral neuropathy. Treatment with interferon alpha may result in NAION. Discontinuation of therapy deserves consideration after weighing individual risks and benefits. PMID:20351572

There is an increasing body of evidence linking the common respiratory human pathogen Chlamydia pneumoniae with atherosclerosis and other vascular disorders. Our research was designed to investigate the association of this organism with anterior ischemic opticneuropathy (AION), representing an acute ischemic disorder of the optic nerve head. Sera were examined of 14 consecutive patients with AION and of 14

Ischemic opticneuropathy is the most common cause of visual complications after non-ophthalmic surgery. The incidence has varied in different case series, but prone-position spine surgery appears to be involved in most of the reports. We present the case of a 47-year-old woman who developed near total blindness in the left eye following lumbar spine fusion surgery involving the loss of 900 mL of blood. An ophthalmic examination including inspection of the ocular fundus, fluorescein angiography, and visual evoked potentials returned a diagnosis of retrolaminar opticneuropathy. Outcome was poor. PMID:18200998

Hereditary opticneuropathies are diseases affecting the optic nerve. The most common are mitochondrial hereditary opticneuropathies, i.e., the maternally inherited Leber's hereditary opticneuropathy (LHON) and dominant optic atrophy (DOA). They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is characterized by an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood-onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1, and 14484/ND6) for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are still limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone). Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising avenue that still needs to be validated. PMID:25132831

A case is described of a patient who developed radiation-induced opticneuropathy 18 months following cobalt-60 irradiation for carcinoma of the left maxillary antrum and ethmoid sinus. This case is unusual because of the early onset of the optic nerve damage following radiation therapy and the ultimate emergence of the eye involved by tumor compression as the better eye in terms of visual acuity.

PURPOSE. To investigate certain biochemical and molecular characteristics of mitochondria in patients with Leber heredi- tary opticneuropathy (LHON)-like opticneuropathies. METHODS. Patients who had LHON-like opticneuropathies in both eyes were selected from neuro-ophthalmology clinics. Evaluation included clinical examination, neuroimaging, and assessment of several mitochondrial parameters in the blood, including sequencing the entire mitochondrial (mt)DNA cod- ing region, measuring

Two patients with mild, adult-onset diabetes mellitus developed a painful ophthalmoplegia and ipsilateral opticneuropathy that was relatively unresponsive to steroids. Histopathological study of the optic nerve of one patient revealed an extensive ischaemic infarct. There was ultimate recovery from the cranial nerve palsies in both patients and the opticneuropathy in one patient. Ischaemic polyneuropathy involving the cranial nerves

Crohn's disease can be accompanied by extraintestinal manifestations. The authors report on a 39-year-old patient who presented with cheilitis granulomatosa as the first manifestation of Crohn's disease. Four years later, intestinal Crohn's disease was diagnosed. One year afterward, acute loss of visual acuity from opticneuropathy developed as another rare extraintestinal manifestation of Crohn's disease. PMID:11960070

Nonarteritic anterior ischemic opticneuropathy (NAION) is the most common clinical presentation of acute ischemic damage to the optic nerve. Most treatments proposed for NAION are empirical and include a wide range of agents presumed to act on thrombosis, on the blood vessels, or on the disc edema itself. Others are presumed to have a neuroprotective effect. Although there have been multiple therapies attempted, most have not been adequately studied, and animal models of NAION have only recently emerged. The Ischemic OpticNeuropathy Decompression Trial (IONDT), the only class I large multicenter prospective treatment trial for NAION, found no benefit from surgical intervention. One recent large, nonrandomized controlled study suggested that oral steroids might be helpful for acute NAION. Others recently proposed interventions are intravitreal injections of steroids or anti-vascular endothelial growth factor (anti-VEGF) agents. There are no class I studies showing benefit from either medical or surgical treatments. Most of the literature on the treatment of NAION consists of retrospective or prospective case series and anecdotal case reports. Similarly, therapies aimed at secondary prevention of fellow eye involvement in NAION remain of unproven benefit. PMID:20006051

This case report describes a 20-yr-old man who presented with retro-orbital pain and blurred vision in his left eye 3 wk after an altitude exposure in a hypobaric chamber. He was found to have significant deficits in color vision and visual fields consistent with an opticneuropathy in his left eye. The patient was diagnosed with decompression sickness and treated with hyperbaric oxygen with a U.S. Navy Treatment Table VI. All signs and symptoms resolved with a single hyperbaric oxygen treatment but recurred. A head MRI revealed a left frontoethmoid sinus opacity. A concomitant sinusitis was diagnosed. The patient had full resolution of symptoms after a total of four hyperbaric oxygen treatments and antibiotic therapy at 6-wk follow-up. Although a para-infectious etiology for this patient's opticneuropathy cannot be excluded, his history of altitude exposure and significant, rapid response to hyperbaric oxygen treatment strongly implies decompression sickness in this case. PMID:14503679

Abstract Traumatic opticneuropathy is a cause of loss of vision associated with head injuries. Treatment options include observation, steroids and decompression of the optic canal. We report a case where the optic canal decompression was performed using a transcaruncular approach under a regional block. The incision was made through the caruncle and the dissection was carried down to the periosteum down to the orbital apex where the optic nerve was seen exiting through the optic canal posterior to the posterior ethmoidal artery. The optic nerve was decompressed with good visualization. Hemostasis and wound closure was achieved using fibrin glue. Postoperatively visual acuity improved with minimal inflammation enabling early rehabilitation. PMID:25208226

Sphenoid sinus mucocele comprises only 2% of all paranasal sinus mucoceles. In literature, there is a case report on sphenoidal mucocele causing bilateral opticneuropathy, with unilateral partial recovery and cranial nerve palsy, but we did not come across any literature with bilateral opticneuropathy and ophthalmoplegia together caused by spheno-ethmoidal mucocele. We present such a rare case of spheno-ethmoidal mucocele causing bilateral opticneuropathy and unilateral sixth nerve palsy who had postsurgery, unilateral good vision recovery, and complete resolution of sixth nerve palsy. PMID:23571243

Contrast sensitivity function was measured by a computer automated method on 38 eyes with dysthyroid opticneuropathy and 34 eyes with Graves' ophthalmopathy only. The results were compared with 74 healthy control eyes. Disturbances of contrast sensitivity functions were found in both groups when compared with controls. The eyes affected with dysthyroid opticneuropathy showed pronounced loss of contrast sensitivity in the low frequency range, which facilitates differentiation between the two groups. PMID:8280684

Five patients with severe dysthyroid opticneuropathy were treated with intravenous methylprednisolone (1 g daily for 3 consecutive days). Before administration, visual acuity of the more severely affected eyes of each patient was counting fingers at 5 feet, 8/200, 20/400, 20/200, and 20/80. Immediately after completion of pulse therapy, visual acuity improved to 20/25 in four patients and 20/30 in one. Remissions were maintained with oral prednisone and external beam irradiation of the orbit. Pulse methylprednisolone therapy appears to be beneficial in the initial management of severe dysthyroid opticneuropathy.

Objectives To compare the optic nerve head (ONH) structure between compressive opticneuropathy (CON) and glaucomatous opticneuropathy (GON), and to determine whether selected ONH quantitative parameters effectively discriminate between GON and CON, especially CON cases presenting with a glaucoma-like disc. Methods We prospectively assessed 34 patients with CON, 34 age-matched patients with moderate or severe GON, and 34 age-matched healthy control subjects. The quantitative parameters of ONH structure were compared using the Heidelberg Retina Tomograph 2 (HRT2) and Spectralis optical coherence tomography with an enhanced depth imaging method. Results The mean and maximum cup depths of CON were significantly smaller than those with GON (P<0.001 and P<0.001, respectively). The distance between Bruch's membrane opening and anterior surface of the lamina cribrosa (BMO-anterior LC) of CON was also significantly smaller than that of glaucoma but was similar to that of the healthy group (P<0.001 and P?=?0.47, respectively). Based on Moorfields regression analysis of the glaucoma classification of HRT2, 15 eyes with CON were classified with a glaucoma-like disc. The cup/disc area ratio did not differ between cases of CON with a glaucoma-like disc and cases of GON (P?=?0.16), but the BMO-anterior LC and mean and maximum cup depths of CON cases with a glaucoma-like disc were smaller than those in GON (P?=?0.005, P?=?0.003, and P?=?0.001, respectively). Conclusions Measurements of the cup depths and the LC depth had good ability to differentiate between CON with a glaucoma-like disc and glaucoma. There was no laminar remodeling detected by laminar surface position in the patients with CON compared to those with GON. PMID:25375855

This article presents results of a noncontrolled clinical study of 20 persons with Leber's hereditary opticneuropathy who were treated from 1976 to 1990 at the Low Vision Centre of the Finnish Federation of the Visually Handicapped. The importance of early functional visual rehabilitation is emphasized, as is the use of low vision aids to help…

A case of ischemic opticneuropathy resulting from uterine hemorrhage is reported in which a 37-year-old white woman, gravida 1, para 0, was diagnosed at 8 weeks' gestation with a ruptured ectopic pregnancy. After diagnostic laparoscopy the patient underwent a minilaparotomy, cornual wedge resection, and right salpingectomy with a total estimated blood loss of 3000 ml. Her postoperative course was

Introduction: Radiation-induced opticneuropathy (RON) is an infrequent but devastating consequence of radiation exposure to the visual pathways, usually following months to years after the treatment of paranasal or intracranial tumours. Hyperbaric oxygen (HBO) therapy is one of several therapies that have been tried for this condition. The purpose of this review is to describe the clinical characteristics of RON,

We report a case of acute, bilateral and severe vision loss after inadvertent consumption of a large quantity of the homoeopathic medication Arnica-30. Severe vomiting which required hospitalization preceded visual symptoms. In the acute stage, pupillary responses to light were absent and fundus examination was normal. Vision loss followed a fluctuating course, with profound loss noted after 6 weeks along with bilateral optic disc pallor. Neuro-ophthalmic examination and detailed investigations were performed, including magnetic resonance imaging, electroretinography (ERG) and visual evoked potentials (VEP). Ocular coherence tomography (OCT) showed gross thinning of the retinal nerve fiber layer. While a differential diagnosis of posterior ischemic opticneuropathy was kept in mind, these findings supported a diagnosis of bilateral toxic opticneuropathy. Arnica-30 is popularly used to accelerate wound healing, including after oculoplastic surgery. While homeopathic medicines are generally considered safe due to the very low concentrations involved, Arnica-30 may be neurotoxic if consumed internally in large quantities. PMID:22877081

Glaucoma is a major cause of worldwide irreversible blindness. The central role of raised intraocular pressure (IOP) is being questioned as many patients continue to demonstrate a clinically downhill course despite initial control of IOP. The latest concept of recognizing glaucoma as a multifactorial, progressive, neurodegenerative disease of retinal ganglion cells (RGCSs) associated with characteristic axon degeneration in the optic nerve emphasizes that several pressure-independent mechanisms are responsible for the development and progression of glaucomatous opticneuropathy. Neuroprotection as a pharmacological strategy to mitigate retinal ganglion cell death has been a popular current approach. The aim of this review is to evaluate the neuroprotective potential of calcium channel blockers in glaucomatous opticneuropathy. PMID:24600641

A previously healthy 34-year-old man sustained multiple skull fractures in a traffic accident. Radiological findings and visual field examination did not detect any abnormality. Shortly after the accident, he noticed blurred vision in both eyes. Six months after the accident, he gradually developed disturbance of visual acuity in the right eye. His best corrected visual acuity (BCVA) was 0.8 OD and 1.2 OS and brain MRI did not show any abnormality, while Humphrey visual field analysis demonstrated right homonymous hemianopsia. Two months after the initial presentation, his BCVA showed 0.1 OD and 0.08 OS. Visual field examination suggested that both right homonymous hemianopsia and left blind spot had become enlarged. Mitochondrial DNA analysis demonstrated G11,778A mutation and a diagnosis of Leber's hereditary opticneuropathy (LHON) was made. A few reports have documented mild acute insult to the head or blunt optic trauma as triggers of opticneuropathy in subjects with LHON. Although, the precise mechanism of LHON following trauma remains unknown, it appears that an acute insult may be sufficient to precipitate neuropathy in the optic nerve already compromised by mitochondrial dysfunction. Asymptomatic carriers should be advised to avoid possible precipitating factors such as head trauma. PMID:22019873

Non-arteritic anterior ischemic opticneuropathy (NA- AION) is a common, visually disabling disorder occurring in the middle-aged and elderly, but no age group is immune to it—in two large series the youngest persons with NA- ION were 18 (1) and 13 (2) years old. NA-AION is a multifactorial disease; several risk factors play a role in its development, some acting

Perioperative ischemic opticneuropathy (ION) after nonocular surgery is a rare complication leading to permanent and often severe vision loss. Due in part to the low prevalence of this complication, there remains no reliable way to predict which patients will develop ION. We present a patient with sequential episodes of unilateral perioperative ION, both occurring after otherwise uncomplicated hip operations. Patients and physicians should be aware that perioperative ION after one surgery may increase the risk of ION after subsequent surgeries. PMID:24621863

Giant axonal neuropathies are a group of acquired and inherited human diseases morphologically characterized by accumulation of neurofilaments (NF) in enlargements of preterminal regions of central and peripheral axons. Slow axonal transport was studied in the optic systems of rats treated with 2,5-hexanedione, a toxic compound that produces an experimental model of giant axonal neuropathy. The transport rate of NF and of two other polypeptides of Mr 64,000 and 62,000 were selectively increased. Other components of the slow axonal transport were not affected. Acceleration of labeled NF was also observed when 2,5-hexanedione was given after [35S]methionine administration. Morphometric analysis revealed that the number of NF and the axon size were decreased in regions of optic axons proximal to the enlargements. It is suggested that acceleration of NF transport leads to a longitudinal redistribution of NF: NF decrease proximally and increase distally, forming NF-containing enlargements. Evidence was obtained that polypeptides of Mr 64,000 and 62,000 are cytoskeletal components related to intermediate filaments, normally migrating with the component a of the slow axonal transport. The 2,5-hexanedione axon may provide insight into the pathogenesis of inherited and acquired giant axonal neuropathies and offers a model to investigate the relationship between number of NF and axonal size in central axons. Images PMID:2579382

Leber's hereditary opticneuropathy is a maternally inherited disease resulting in optic nerve degeneration and cardiac dysrhythmia. A mitochondrial DNA replacement mutation was identified that correlated with this disease in multiple families. This mutation converted a highly conserved arginine to a histidine at codon 340 in the NADH dehydrogenase subunit 4 gene and eliminated an Sfa NI site, thus providing a simple diagnostic test. This finding demonstrated that a nucleotide change in a mitochondrial DNA energy production gene can result in a neurological disease.

Leber hereditary opticneuropathy (LHON) and autosomal-dominant optic atrophy (DOA) are the two most common inherited opticneuropathies in the general population. Both disorders share striking pathological similarities, marked by the selective loss of retinal ganglion cells (RGCs) and the early involvement of the papillomacular bundle. Three mitochondrial DNA (mtDNA) point mutations; m.3460G>A, m.11778G>A, and m.14484T>C account for over 90% of LHON cases, and in DOA, the majority of affected families harbour mutations in the OPA1 gene, which codes for a mitochondrial inner membrane protein. Optic nerve degeneration in LHON and DOA is therefore due to disturbed mitochondrial function and a predominantly complex I respiratory chain defect has been identified using both in vitro and in vivo biochemical assays. However, the trigger for RGC loss is much more complex than a simple bioenergetic crisis and other important disease mechanisms have emerged relating to mitochondrial network dynamics, mtDNA maintenance, axonal transport, and the involvement of the cytoskeleton in maintaining a differential mitochondrial gradient at sites such as the lamina cribosa. The downstream consequences of these mitochondrial disturbances are likely to be influenced by the local cellular milieu. The vulnerability of RGCs in LHON and DOA could derive not only from tissue-specific, genetically-determined biological factors, but also from an increased susceptibility to exogenous influences such as light exposure, smoking, and pharmacological agents with putative mitochondrial toxic effects. Our concept of inherited mitochondrial opticneuropathies has evolved over the past decade, with the observation that patients with LHON and DOA can manifest a much broader phenotypic spectrum than pure optic nerve involvement. Interestingly, these phenotypes are sometimes clinically indistinguishable from other neurodegenerative disorders such as Charcot-Marie-Tooth disease, hereditary spastic paraplegia, and multiple sclerosis, where mitochondrial dysfunction is also thought to be an important pathophysiological player. A number of vertebrate and invertebrate disease models has recently been established to circumvent the lack of human tissues, and these have already provided considerable insight by allowing direct RGC experimentation. The ultimate goal is to translate these research advances into clinical practice and new treatment strategies are currently being investigated to improve the visual prognosis for patients with mitochondrial opticneuropathies. PMID:21112411

Our current understanding of Leber’s hereditary opticneuropathy (LHON)-mitochondrial connection falls short of comprehensive. Twenty years of intensive investigation have yielded a wealth of information about mitochondria, the mitochondrial genome, the metabolism of the optic nerve and other structures, and the phenotypic variability of classic LHON. However, we still cannot completely explain how primary LHON mutations injure the optic nerve or why the optic nerve is particularly at risk. We cannot explain the incomplete penetrance or the male predominance of LHON, the typical onset in young adult life without warning, or the synchronicity of visual loss. Moreover, primary LHON mutations clearly are not present in every family with the LHON phenotype (including multigenerational maternal inheritance), and they are present in only a minority of individuals who have the LHON opticneuropathy phenotype without a family history. All lines of evidence point to abnormalities of the mitochondria as the direct or indirect cause of LHON. Therefore, the mitochondria-LHON connection needs to be revisited and examined closely. This review will attempt to do that and provide an update on various aspects of LHON. PMID:21572729

Our current understanding of Leber's hereditary opticneuropathy (LHON)-mitochondrial connection falls short of comprehensive. Twenty years of intensive investigation have yielded a wealth of information about mitochondria, the mitochondrial genome, the metabolism of the optic nerve and other structures, and the phenotypic variability of classic LHON. However, we still cannot completely explain how primary LHON mutations injure the optic nerve or why the optic nerve is particularly at risk. We cannot explain the incomplete penetrance or the male predominance of LHON, the typical onset in young adult life without warning, or the synchronicity of visual loss. Moreover, primary LHON mutations clearly are not present in every family with the LHON phenotype (including multigenerational maternal inheritance), and they are present in only a minority of individuals who have the LHON opticneuropathy phenotype without a family history. All lines of evidence point to abnormalities of the mitochondria as the direct or indirect cause of LHON. Therefore, the mitochondria-LHON connection needs to be revisited and examined closely. This review will attempt to do that and provide an update on various aspects of LHON. PMID:21572729

Opticneuropathy induced by radiation is an infrequent cause of delayed visual loss that may at times be difficult to differentiate from compression of the visual pathways by recurrent neoplasm. The authors describe six patients with this disorder who experienced loss of vision 6 to 36 months after neurological surgery and radiation therapy. Of the six patients in the series, two had a pituitary adenoma and one each had a metastatic melanoma, multiple myeloma, craniopharyngioma, and lymphoepithelioma. Visual acuity in the affected eyes ranged from 20/25 to no light perception. Magnetic resonance (MR) imaging showed sellar and parasellar recurrence of both pituitary adenomas, but the intrinsic lesions of the optic nerves and optic chiasm induced by radiation were enhanced after gadolinium-diethylenetriaminepenta-acetic acid (DTPA) administration and were clearly distinguishable from the suprasellar compression of tumor. Repeated MR imaging showed spontaneous resolution of gadolinium-DTPA enhancement of the optic nerve in a patient who was initially suspected of harboring recurrence of a metastatic malignant melanoma as the cause of visual loss. The authors found the presumptive diagnosis of radiation-induced opticneuropathy facilitated by MR imaging with gadolinium-DTPA. This neuro-imaging procedure may help avert exploratory surgery in some patients with recurrent neoplasm in whom the etiology of visual loss is uncertain.

Sixteen patients (14 women and two men) with dysthyroid opticneuropathy (26 involved eyes) were treated with either oral corticosteroids, orbital irradiation, surgical orbital decompression, combined corticosteroids and irradiation, or combined corticosteroids and surgical decompression. Thirteen of 16 eyes responded favorably to corticosteroid therapy but eight of the 13 relapsed upon discontinuation of treatment. Two of four eyes responded to irradiation initially but later relapsed. The response to orbital decompression was almost uniformly beneficial (eight of nine eyes responded) and lasting in all. Combined modes of therapy offered no additional advantage.

Thrombotic microangiopathies (TMAs) are a group of disorders characterized by occurrence of thrombi of fibrin and/or platelets with microvascular occlusion and organ ischemia especially the kidney and brain. Hemolysis with a microangiopathic blood smear, elevated liver enzymes, and low platelet count (HELLP syndrome) is a type of TMA peculiar to pregnancy and may be associated with neurological complications. Visual complications in HELLP are usually related to cortical blindness. We present the first case of HELLP associated with bilateral anterior ischemic opticneuropathy (AION) and blindness which resolved with plasma exchange. PMID:25328716

Leber's hereditary opticneuropathy (LHON), a typical maternally inherited disease, is caused by a single nucleotide change of G to A at the site of nucleotide 11,788 of mtDNA. We used PCR method to analysis mtDNA from 102 individuals of nineteen pedigrees. The results showed that 67% of the patients (30/45) and 55% (29/53) of the maternal relatives have such a mutation, while no mutation exists in the four normal individuals. The results show that Wallace's mutation is a main cause of LHON in China. PMID:7994643

We studied the accuracy of B-scan ultrasonography to diagnose radiation-induced opticneuropathy in 15 patients with uveal melanoma. Opticneuropathy was diagnosed by an observer masked as to clinical and photographic data. We analyzed planimetry area measurements of the retrobulbar nerve before and after irradiation. The retrobulbar area of the optic nerve shadow on B-scan was quantitated with a sonic digitizer. Increased optic nerve shadow area was confirmed in 13 of 15 patients who had radiation opticneuropathy (P less than .004). The correct diagnosis was confirmed when the results of ultrasound were compared to fundus photography and fluorescein angiography. In 13 patients there was acute radiation opticneuropathy. Two patients did not show an enlarged retrobulbar optic nerve, and the clinical appearance suggested early progression to optic atrophy. Ultrasonography documents the enlargement of the optic nerve caused by acute radiation changes.

Bilateral visual loss secondary to inherited opticneuropathies is an important cause of registrable blindness among children and young adults. The two prototypal disorders seen in clinical practice are Leber hereditary opticneuropathy (LHON) and autosomal dominant optic atrophy (DOA). About 90% of LHON cases are due to one of three mitochondrial DNA (mtDNA) point mutations: m.3460G>A, m.11778G>A, and m.14484T>C, which affect critical complex I subunits of the mitochondrial respiratory chain. The majority of patients with DOA harbour pathogenic mutations within OPA1, a nuclear gene that codes for a multifunctional inner mitochondrial membrane protein. Despite their contrasting genetic basis, LHON and DOA share overlapping pathological and clinical features that serve to highlight the striking tissue-specific vulnerability of the retinal ganglion cell (RGC) layer to disturbed mitochondrial function. In addition to severe visual loss secondary to progressive optic nerve degeneration, a subgroup of patients will also develop a more aggressive syndromic phenotype marked by significant neurological deficits. The management of LHON and DOA remains largely supportive, but major advances in our understanding of the mechanisms underpinning RGC loss in these two disorders are paving the way for novel forms of treatment aimed at halting or reversing visual deterioration at different stages of the disease process. In addition to neuroprotective strategies for rescuing RGCs from irreversible cell death, innovative in vitro fertilisation techniques are providing the tantalising prospect of preventing the germline transmission of pathogenic mtDNA mutations, eradicating in so doing the risk of disease in future generations. PMID:24603424

Summary Leber's hereditary opticneuropathy (LHON) is a rare mitochondrial retinopathy, caused by mutations in subunits of complex I of the respiratory chain, which leads to elevated levels of oxidative stress and an insufficient energy supply. This molecular pathology is thought to be responsible for the dysfunction and eventual apoptotic loss of retinal ganglion cells in the eye, which ultimately results in blindness. Many strategies, ranging from neuroprotectants, antioxidants, anti-apoptotic- and anti-inflammatory compounds have been tested with mixed results. Currently, the most promising compounds are short-chain quinones that have been shown to protect the vision of LHON patients during the early stages of the disease. This commentary gives a brief overview on the current status of tested therapeutics and also addresses future developments such as the use of gene therapy that hopefully will provide safe and efficient therapy options for all LHON patients. PMID:25343117

We have performed an entire-population-based survey of the epidemiology and penetrance of Leber hereditary opticneuropathy (LHON) in Finland - a country that is among the best-studied genetic isolates in the world. During our long-term clinical follow-up period since 1970, we have so far identified 36 LHON families in Finland, comprised of almost 1000 family members. Counting the unaffected family members has been possible thanks to accessible genealogical records, and this has improved the accuracy of our penetrance figures by minimizing the sample bias. Our results, although confirming some well-known features of LHON, indicate that the overall penetrance of LHON is lower than previously estimated, and that affected females have a higher incidence of affected offspring compared to the unaffected females. The prevalence of LHON in Finland is 1:50 000, and one in 9000 Finns is a carrier of one of the three LHON primary mutations. PMID:17406640

Posterior ischaemic neuropathy (PION) is characterized by infarction in the retrobulbar optic nerve. A 73-year-old man suddenly experienced blurred vision in his left eye and intermittent weakness in his right hand. He had visual defects of superior lateral quarter and inferior medial quarter areas in the left eye. Gadolinium-enhanced magnetic resonance imaging (MRI) revealed segmental enhancement in the left optic

The development of biopharmaceutical agents, including the interferons (IFN), offers new treatment options for a wide range of medical conditions. Such advancements, however, have not come without risk to patients. Opticneuropathy in the setting of IFN therapy has been previously documented and is usually attributed to anterior ischaemic opticneuropathy; however, the pathophysiology remains poorly understood. Retrobulbar opticneuropathy associated with IFN treatment has not been described in the medical literature to date. We report the case of a 38-year-old Caucasian female with refractory acute myeloid leukaemia who developed painless bilateral blurred vision within 2 weeks of commencing a course of IFN alpha-2a. Extensive clinical workup demonstrated bilateral retrobulbar opticneuropathy. We report the clinical evaluation of this first documented case and discuss the possible aetiologies of her presentation. PMID:25298771

Leber’s hereditary opticneuropathy (LHON) is characterized by retinal ganglion cell (RGC) degeneration with the preferential involvement of those forming the papillomacular bundle. The optic nerve is considered the main pathological target for LHON. Our aim was to investigate the possible involvement of the post-geniculate visual pathway in LHON patients. We used diffusion-weighted imaging for in vivo evaluation. Mean diffusivity maps from 22 LHON visually impaired, 11 unaffected LHON mutation carriers and 22 healthy subjects were generated and compared at level of optic radiation (OR). Prefrontal and cerebellar white matter were also analyzed as internal controls. Furthermore, we studied the optic nerve and the lateral geniculate nucleus (LGN) in post-mortem specimens obtained from a severe case of LHON compared to an age-matched control. Mean diffusivity values of affected patients were higher than unaffected mutation carriers (P<0.05) and healthy subjects (P<0.01) in OR and not in the other brain regions. Increased OR diffusivity was associated with both disease duration (B?=?0.002; P<0.05) and lack of recovery of visual acuity (B?=?0.060; P<0.01). Post-mortem investigation detected atrophy (41.9% decrease of neuron soma size in the magnocellular layers and 44.7% decrease in the parvocellular layers) and, to a lesser extent, degeneration (28.5% decrease of neuron density in the magnocellular layers and 28.7% decrease in the parvocellular layers) in the LHON LGN associated with extremely severe axonal loss (99%) in the optic nerve. The post-geniculate involvement in LHON patients is a downstream post-synaptic secondary phenomenon, reflecting de-afferentation rather than a primary neurodegeneration due to mitochondrial dysfunction of LGN neurons. PMID:23209682

Although the diagnosis of Graves' orbitopathy is primarily made clinically based on laboratory tests indicative of thyroid dysfunction and autoimmunity, imaging studies, such as computed tomography, magnetic resonance imaging, ultrasound and color Doppler imaging, play an important role both in the diagnosis and follow-up after clinical or surgical treatment of the disease. Imaging studies can be used to evaluate morphological abnormalities of the orbital structures during the diagnostic workup when a differential diagnosis versus other orbital diseases is needed. Imaging may also be useful to distinguish the inflammatory early stage from the inactive stage of the disease. Finally, imaging studies can be of great help in identifying patients prone to develop dysthyroid opticneuropathy and therefore enabling the timely diagnosis and treatment of the condition, avoiding permanent visual loss. In this paper, we review the imaging modalities that aid in the diagnosis and management of Graves' orbitopathy, with special emphasis on the diagnosis of optic nerve dysfunction in this condition. PMID:23184212

Leber's hereditary opticneuropathy is a rare genetic disorder affecting the retinal ganglion cells leading to a persistent severe bilateral loss of visual acuity within weeks or months. Males are much more likely to be affected than females, disease onset in most cases takes place between age 15 and 35 years. The disease is caused by point mutations in the mitochondrial DNA. The penetrance of the disease is incomplete, i.e., not all mutation carriers develop clinical symptoms. The phenotype is relatively uniform, but age at onset, severity and prognosis may vary even within the same family. Environmental and endocrine factors, optic disc anatomy as well as mitochondrial and nuclear genetic factors are discussed to influence penetrance as well as interindividual and intrafamilial variability. However, only cigarette smoking and excessive alcohol consumption have been shown to trigger disease onset. The disease is characterised by a central visual field defect, impaired colour vision and fundoscopically a peripapillary microangiopathy in the acute phase. Most patients end up after some months with a severe visual loss below 0.1 and in most cases there is no significant improvement of visual acuity in the course. In rare cases patients experience a mostly partial visual recovery which depends on the type of mutation. For confirmation of the diagnosis a detailed ophthalmological examination with fundoscopy, family history and genetic analysis of the mitochondrial DNA is needed. To date, there is no proven causal therapy, but at early disease stages treatment with idebenone can be tried. PMID:24658858

Many human childhood mitochondrial disorders result from abnormal mitochondrial DNA (mtDNA) and altered bioenergetics. These abnormalities span most of the mtDNA, demonstrating that there are no "unique" positions on the mitochondrial genome that when deleted or mutated produce a disease phenotype. This diversity implies that the relationship between mitochondrial genotype and clinical phenotype is very complex. The origins of clinical phenotypes are thus unclear, fundamentally difficult-to-treat, and are usually clinically devastating. Current treatment is largely supportive and the disorders progress relentlessly causing significant morbidity and mortality. Vitamin supplements and pharmacological agents have been used in isolated cases and clinical trials, but the efficacy of these interventions is unclear. In spite of recent advances in the understanding of the pathogenesis of mitochondrial diseases, a cure remains elusive. An optimal cure would be gene therapy, which involves introducing the missing gene(s) into the mitochondria to complement the defect. Our recent research results indicate the feasibility of an innovative protein-transduction ("protofection") technology, consisting of a recombinant mitochondrial transcription factor A (TFAM) that avidly binds mtDNA and permits efficient targeting into mitochondria in situ and in vivo. Thus, the development of gene therapy for treating mitochondrial disease offers promise, because it may circumvent the clinical abnormalities and the current inability to treat individual disorders in affected individuals. This review aims to focus on current treatment options and future therapeutics in mitochondrial disease treatment with a special emphasis on Leber's hereditary opticneuropathy. PMID:23545042

Background To describe the first reported case of toxic opticneuropathy secondary to docetaxel (Taxotere®) chemotherapy. Case presentation A 53-year-old female presented with predominantly unilateral visual loss, but extensive bilateral visual field defects and bilateral optic nerve head swelling 2 weeks after first dose of docetaxel (Taxotere®) and trastuzumab (Herceptin®) chemotherapy for a left sided node-positive, HER2 positive breast cancer. Extensive investigation ruled out other causes of opticneuropathy. She was treated with high dose corticosteroids intravenously for 1 week then a tapering oral dose over 8 weeks. Visual field defects gradually resolved and visual acuity improved. Docetaxel chemotherapy was discontinued but targeted therapy with trastuzumab continued without further complication. Conclusion Docetaxel can cause a toxic opticneuropathy possibly due to an ischemic or neurotoxic mechanism at the optic nerve head. With cessation of docetaxel therapy and treatment with systemic corticosteroids, visual recovery can occur without significant residual visual deficit. PMID:24564293

Four patients with radiation-induced opticneuropathies were treated with hyperbaric oxygen. They had received radiation therapy for treatment of pituitary tumors, reticulum cell sarcoma, and meningioma. Two presented with amaurosis fugax before the onset of unilateral visual loss and began hyperbaria within 72 hours after development of unilateral opticneuropathy. Both had return of visual function to baseline levels. The others initiated treatment two to six weeks after visual loss occurred in the second eye and had no significant improvement of vision. Treatment consisted of daily administration of 100% oxygen under 2.8 atmospheres of pressure for 14-28 days. There were no medical complications of hyperbaria. While hyperbaric oxygen is effective in the treatment of radiation-induced opticneuropathy, it must be instituted within several days of deterioration in vision for restoration of baseline function.

To investigate the risk of radiation-induced opticneuropathy according to total radiotherapy dose and fraction size, based on both retrospective and prospectively collected data. Between October 1964 and May 1989, 215 optic nerves in 131 patients received fractionated external-beam irradiation during the treatment of primary extracranial head and neck tumors. All patients had a minimum of 3 years of ophthalmologic follow-up (range, 3 to 21 years). The clinical end point was visual acuity of 20/100 or worse as a result of optic nerve injury. Anterior ischemic opticneuropathy developed in five nerves (at mean and median times of 32 and 30 months, respectively, and a range of 2-4 years). Retrobulbar opticneuropathy developed in 12 nerves (at mean and median times of 47 and 28 months, respectively, and a range of 1-14 years). No injuries were observed in 106 optic nerves that received a total dose of <59 Gy. Among nerves that received doses of {ge} 60 Gy, the dose per fraction was more important than the total dose in producing opticneuropathy. The 15-year actuarial risk of optic compared with 47% when given in fraction sizes {ge}1.9 Gy. The data also suggest an increased risk of optic nerve injury with increasing age. As there is no effective treatment of radiation-induced opticneuropathy, efforts should be directed at its prevention by minimizing the total dose, paying attention to the dose per fraction to the nerve, and using reduced field techniques where appropriate to limit the volume of tissues that receive high-dose irradiation. 32 refs., 5 figs., 5 tabs.

During 1992 and 1993 an epidemic of optic and peripheral neuropathy affected over 50,000 Cubans. This occurred in the unique setting of a communist country which had a widespread health care network and wherein sudden changes in the economy affected most of the population. Although nutritional factors appeared to play a key role in the pathogenesis of the epidemic neuropathy, viral, toxic, and genetic factors were investigated by Cuban and North American scientists. The authors, representing different disciplines and different groups that visited Cuba during the epidemic, review and reflect on the clinical and laboratory findings which became available through their own experience and through reviewing the literature. The recent Cuban epidemic is compared to similar outbreaks of optic and peripheral neuropathy which have occurred in the past. PMID:9104771

Purpose To quantify the morphological features of the optic nerve head using radial polynomials, to use these morphometric models as the basis for classification of glaucomatous opticneuropathy glaucomatous opticneuropathy via an automated decision tree induction algorithm, and to compare these classification results with established methods. Methods A cohort of patients with high-risk ocular hypertension or early glaucoma (n = 179) and a second cohort of normal subjects (n = 96) were evaluated for glaucomatous opticneuropathy using stereographic disc photography and confocal scanning laser tomography. Morphological features of the optic nerve head region were modeled from the tomography data using pseudo-Zernike radial polynomials and features derived from these models were used as the basis for classification by a decision tree induction algorithm. Decision tree classification performance was compared with expert classification of stereographic disc photos and analysis of neural retinal rim thickness by Moorfields Regression Analysis (MRA). Results Root mean squared (RMS) error of the morphometric models decreased asymptotically with additional polynomial coefficients, from 62 ± 0.5 ?m (32 coefficients) to 32 ± 5.7 ?m (256 coefficients). Optimal morphometric classification was derived from a subset of 64 total features and had low sensitivity (69%), high specificity (88%), very good accuracy (80%), and area under the ROC curve (AUROC) was 88% (95% CI = 78 to 98%). By comparison, MRA classification of the same records had a comparatively poorer sensitivity (55%), but had higher specificity (95%), with similar overall accuracy (78%) and AUROC curve, 83% (95 % CI = 70 to 96%). Conclusions Pseudo-Zernike radial polynomials provide a mathematically compact and faithful morphological representation of the structural features of the optic nerve head. This morphometric method of glaucomatous opticneuropathy classification has greater sensitivity, and similar overall classification performance (AUROC) when compared with classification by neural retinal rim thickness by MRA in patients with high-risk ocular hypertension and early glaucoma. PMID:21423035

A 53-year-old man with a history of alcoholism since 10 years admitted for jaundice elsewhere developed bilateral simultaneous decrease in vision in both the eyes 4 days after admission. His best-corrected visual acuity was 20/20 in both eyes. Visual field evaluation revealed an inferior altitudinal defect in both the eyes. Optic disc appearance, visual fields, and optical coherence tomography of discs were suggestive of nonarteritic anterior ischemic opticneuropathy (NAION) in both the eyes. Liver function tests revealed elevated serum bilirubin and hepatic enzymes. He was negative for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Abdominal ultrasound revealed no focal hepatic lesion, and carotid doppler revealed no arteriosclerosis. A diagnosis of bilateral ischemic opticneuropathy associated with alcoholic hepatitis was made. Bilateral simultaneous NAION has been previously reported in perioperative visual loss, HCV infection, and interferon treatment. This is the first case report of bilateral simultaneous NAION in alcoholic hepatitis in the absence of associated infective viral hepatitis. We explore the pathophysiology of ischemic opticneuropathy in liver disease. An early intervention to correct the risk factors leading to NAION may help in preventing this vision-threatening complication in patients with chronic liver disease. PMID:25136231

Although Alzheimer's disease (AD) has been shown to be associated with a true primary opticneuropathy, the underlying pathophysiology of this disease and in particular the optic nerve disorder is still poorly understood. The receptor for advanced glycation end products (RAGE) has been implicated in the pathogenesis of AD by mediating the transport of plasma amyloid-beta into the brain. Once ligated, RAGE can play a role in signal transduction, leading to amplification and perpetuation of inflammatory processes. As a key player in the reaction to CNS injury, astrocytes have been shown to associate with RAGE in a number of diseases, including AD. To investigate the role of RAGE and astrocytes in the pathogenesis of AD opticneuropathy, we conducted immunohistochemical studies to examine the presence of RAGE in donor eyes from patients with AD (n = 10) and controls (n = 3). Both qualitative observation and quantitative analyses using imaging software were used to document the extent of RAGE in the neural tissues. The intensity and extent of RAGE expression was more prominent in AD nerves compared to controls (P < 0.05). The RAGE immunoreactivity was observed in the microvasculature and in close proximity to astrocytic processes. While RAGE immunoreactivity increased with age, the increase was more precipitous in the AD group compared to the controls. The up-regulation of RAGE in the AD optic nerves indicates that RAGE may play a role in the pathophysiology of AD opticneuropathy. PMID:19277685

This case report details an association of the use of over-the-counter sexual enhancement supplements with atypical opticneuropathy. A 42-year-old man presented with right-sided headache and vision loss of the right eye, which deteriorated to a single quadrant of hand motion over 11 days. Serial orbital magnetic resonance imaging scans demonstrated progressive orbital optic nerve enhancement extending into the optic canal despite high-dose steroid treatment. The patient eventually admitted to using several over-the-counter sexual enhancement supplements prior to the onset of symptoms and throughout the course of his steroid treatment, which he subsequently discontinued. His vision improved to 20/200 with an expanded visual field. Anterior ischemic opticneuropathy has been reported in association with phosphodiesterase (PDE)-5 inhibitor use, but visual loss in association with unregulated sexual enhancement supplements has not been studied. While one case cannot establish association, our case is suggestive of potential dangers of over-the-counter sexual enhancement supplements, which may contain PDE-5 inhibitors, “male hormones,” and “substances that enhance blood production.” The case also underscores the importance of obtaining a careful history of supplements in patients with opticneuropathies. PMID:25378904

The authors report a case of one patient from a family carrying the homoplasmic Leber hereditary opticneuropathy (LHON) G11778A mitochondrial DNA mutation with papilloedema 9 months prior to the acute stage of LHON and still present at the onset of visual loss. During the vision loss, the MRI demonstrated a T2 hyperintensity and an enhancement of the prechiasmal left

The standard scientific method requires that you make an interesting observation, generate a hypothesis and then design an experiment to test the hypothesis. In ophthalmology, as in most fields of medicine, the observations and hypotheses tend to have more degrees of freedom, and the interpretation of experiments is also more complicated and often indeterminate. But sometimes it works out, going back and forth from bench to bedside to bench, in reiterative cycles. A successful example of alternating bench and bedside studies was presented (AAS) at the 2012 Alper Memorial given at the Washington Hospital Medical Center, illustrating a series of questions and investigations that pertain to mitochondrial opticneuropathies, beginning two decades ago, before the concept of mitochondrial opticneuropathies had much meaning. Basic science questions are often best answered by that extraordinary experiment of nature that we call clinical disease, and clinical questions are often best tested in the laboratory. PMID:23433229

Acute ischemic lesions of the posterior optic nerve and optic tract can produce a variety of visual field defects. A 71-year-old woman presented with acute hemianopia, which led to rt-PA thrombolysis for suspected posterior cerebral artery ischemia. 3-Tesla cMRI, however, revealed the cause to be an acute posterior ischemic opticneuropathy. Cases like this may be more common than thought and quite regularly overlooked in clinical practice, especially when there is no high-resolution MRI available. This case strengthens the importance of repeat MR imaging in patients with persistent visual field defects. PMID:23185170

Multiple sclerosis (MS) and Leber's hereditary opticneuropathy (LHON) have been found to occur in combination. Based on\\u000a an extensive literature search and on a clinical analysis of 55 LHON pedigrees (103 patients) and 40 patients with definite\\u000a MS, this study concludes that the association of LHON and MS is more than a coincidence, and that carrying a primary LHON

Major advances in understanding the pathogenesis of inherited metabolic disease caused by mitochondrial DNA mutations have yet to translate into treatments of proven efficacy. Leber's hereditary opticneuropathy is the most common mitochondrial DNA disorder causing irreversible blindness in young adult life. Anecdotal reports support the use of idebenone in Leber's hereditary opticneuropathy, but this has not been evaluated in a randomized controlled trial. We conducted a 24-week multi-centre double-blind, randomized, placebo-controlled trial in 85 patients with Leber's hereditary opticneuropathy due to m.3460G>A, m.11778G>A, and m.14484T>C or mitochondrial DNA mutations. The active drug was idebenone 900 mg/day. The primary end-point was the best recovery in visual acuity. The main secondary end-point was the change in best visual acuity. Other secondary end-points were changes in visual acuity of the best eye at baseline and changes in visual acuity for both eyes in each patient. Colour-contrast sensitivity and retinal nerve fibre layer thickness were measured in subgroups. Idebenone was safe and well tolerated. The primary end-point did not reach statistical significance in the intention to treat population. However, post hoc interaction analysis showed a different response to idebenone in patients with discordant visual acuities at baseline; in these patients, all secondary end-points were significantly different between the idebenone and placebo groups. This first randomized controlled trial in the mitochondrial disorder, Leber's hereditary opticneuropathy, provides evidence that patients with discordant visual acuities are the most likely to benefit from idebenone treatment, which is safe and well tolerated. PMID:21788663

PURPOSE To study the integrity of inner and outer retinal layers in patients with various types of opticneuropathy by using high-resolution imaging modalities. METHODS Three high-resolution imaging systems constructed at the University of California Davis were used to acquire retinal images from patients with opticneuropathy: (1) adaptive optics (AO)-flood–illuminated fundus camera, (2) high-resolution Fourier domain optical coherence tomography (FDOCT), and (3) adaptive optics-Fourier domain optical coherence tomography (AO-FDOCT). The AO fundus camera provides en face images of photoreceptors whereas cross-sectional images (B-scans) of the retina are obtained with both FDOCT and AO-FDOCT. From the volumetric FDOCT data sets, detailed thickness maps of a three-layer complex consisting of the nerve fiber (NF), ganglion cell (GC), and inner plexiform (IP) layers were created. The number of visible cones in the en face images of photoreceptors was then compared with visual sensitivity maps from Humphrey visual field (HVF; Carl Zeiss Meditec, Inc., Dublin, CA) testing, as well as FDOCT and AO-FDOCT images, including the thickness maps of the NF–GC–IP layer complex. Five types of opticneuropathy were studied: (1) optic neuritis with multiple sclerosis (MS), (2) idiopathic intracranial hypertension (pseudotumor cerebri), (3) nonarteritic anterior ischemic opticneuropathy (NAION), (4) optic nerve head drusen with NAION, and (5) systemic lupus erythematosus with MS and arthritis. RESULTS With permanent visual field loss and thinning of the NF–GC–IP layer complex, cone photoreceptors showed structural changes, making them less reflective, which caused the appearance of dark spaces in the en face images (hence, reduced number of visible cones) and indistinct outer retinal layers in OCT images. However, when the visual field loss was only transient, with a normal NF–GC–IP layer complex, there were no detectable abnormalities in cone photoreceptors (i.e., they were densely packed and had distinct photoreceptor layering in the OCT images). CONCLUSIONS Cone photoreceptors show structural changes when there is permanent damage to overlying inner retinal layers. There was a positive relation between the thickness of the three-layer inner retinal complex, visual sensitivity, and integrity of the cone mosaic. PMID:18436843

In this study, 16 patients (19 eyes) with nonarteritic anterior ischemic opticneuropathy in the acute stage (within 4 weeks) and resolving stage (after 12 weeks) were diagnosed by a series of complete ophthalmic examinations, including fundus examination, optical coherence tomography and fluorescein fundus angiography, and visual field defects were measured with standard automated perimetry. The contralateral uninvolved eyes were used as controls. The retinal nerve fiber layer thickness was determined by optical coherence tomography which showed that the mean retinal nerve fiber layer thickness and the retinal nerve fiber layer thickness from temporal, superior, nasal and inferior quadrants were significantly higher for all measurements in the acute stage than the corresponding normal values. In comparison, the retinal nerve fiber layer thickness from each optic disc quadrant was found to be significantly lower when measured at the resolving stages, than in the control group. Statistical analysis on the correlation between optic disc nerve fiber layer thickness and visual defects demonstrated a positive correlation in the acute stage and a negative correlation in the resolving stage. Our experimental findings indicate that optical coherence tomography is a useful diagnostic method for nonarteritic anterior ischemic opticneuropathy and can be used to evaluate the effect of treatment.

PURPOSE: Leber's hereditary opticneuropathy (LHON), though known to be due to 1 of 3 pathogenic mtDNA point mutations (nucleotide positions 11,778, 3460, and 14,484), usually manifests itself acutely in young adulthood with a stereotypical presentation of dyschromatopsia, loss of central vision, and loss of the papillomacular bundle nerve fiber layer. Histopathologic investigations have demonstrated devastating losses of axons with relative sparing of the most peripherally placed fibers in the optic nerves. This study was designed to morphometrically investigate the nerve fiber spectrum from ultrastructural studies of optic nerves obtained from 2 patients with LHON. METHODS: Two cases of LHON were molecularly characterized and the optic nerves from these cases studied by light microscopy and electron microscopy. Montages were made of electron micrographs cut orthogonal to fibers obtained from the periphery of each optic nerve, and these were then used for the measurement of each axon (short and long axis) and its myelin sheath. From this, a spectrum of nerve fiber layer was generated, yielding axon caliber profiles that could be compared between optic nerves. RESULTS: The total depletion of optic nerve fiber population in the 2 cases of LHON varied from 95% to 99%. Those fibers that were spared were limited to the peripheral optic nerve. The nerve fiber layer spectra of these remaining fibers showed a marked diminution of the first peak of axons of less than 1 micron in diameter, with relative emphasis of a second peak of axons of about 2 microns in diameter. In comparison to normal controls, this reflected a preferential loss of the smallest axons corresponding to the P-cell population. CONCLUSIONS: The clinical features of dyschromatopsia and central scotoma (with preservation of pupils) in LHON suggests the selective loss of the P-cell population known to subserve these (and not pupil) functions. This also correlates well with the fundus findings of early losses of the papillomacular bundle. The present study extends these findings to demonstrate a relative preservation of the M-cells in the optic nerve as reflected by the nerve fiber spectral profile. This selective loss of smaller fibers and their corresponding smaller retinal ganglion cells may, in addition to explaining the clinical features in LHON, provide valuable insights as to the exact pathophysiologic mechanisms by which mitochondrial impairment may induce apoptosis in vulnerable neurons. Images FIGURE 1A FIGURE 1B FIGURE 2A FIGURE 2B FIGURE 3A FIGURE 3B FIGURE 4 A FIGURE 4 B FIGURE 4 C FIGURE 4 D FIGURE 4 E FIGURE 4 F PMID:11190025

Background Non-arteritic anterior ischemic opticneuropathy (N-AION) is caused by acute ischemic infarction of the optic nerve head,\\u000a supplied by the posterior ciliary arteries. Thrombophilia is the tendency\\/predisposition to vascular thromboses of arteries\\u000a and veins, and the existence of thrombophilic risk factors leads to blood hypercoagulability and potentially increased risk\\u000a for thromboses.\\u000a \\u000a \\u000a \\u000a \\u000a Objectives To investigate whether there is an association between N-AION

Background To characterize macular thickness (MT) changes in Leber’s hereditary opticneuropathy (LHON) patients by cirrus HD-optical coherence tomography (OCT), and to study the correlation between MT and best corrected visual acuity (BCVA). Methods Fifty-two eyes from 52 consecutive LHON patients and 14 eyes from 14 age- and sex-matched healthy controls were scanned by OCT. Affected eyes were classified into five groups according to disease duration (1st group: ?3 months; 2nd group: 3–6 months; 3rd group: 6–9 months; 4th group: 9–12 months; and 5th group: >12 months). MT was compared and analyzed. The correlation between BCVA and MT was calculated. Results Less than six months after LHON onset, the cube average thickness (CAT) and the MT in the superior, nasal, inferior, and temporal quadrants of the inner ring and the MT in the nasal quadrant of the outer ring were decreased (P?0.005); at 3–6 months onset, the MT of the temporal quadrants of the outer ring was decreased (P?=?0.045); after 6 months, the MT was significantly thinner in all measurements (P?0.01) except for the central ring. The BCVA was significantly different between each group and controls (P?0.05), but there was no significant correlation among the five groups (P?=?0.666). There was no significant correlation between the BCVA and CAT (P?=?0.893). Conclusions The MT thinned before the retinal nerve fiber layer and this occurred with a particular sequence. Our results provide potential diagnostic information for LHON. PMID:25179213

Purpose: To analyze the parameters that influence the risk of radiation-induced opticneuropathy (RION) after radiotherapy for head-and-neck tumors. Methods and Materials: Between 1964 and 2000, 273 patients with tumors of the nasopharynx, paranasal sinuses, nasal cavity, and hard palate adenoid cystic carcinomas were treated with curative intent and had radiation fields that included the optic nerves and/or chiasm. Patients were followed for at least 1 year after radiotherapy. Results: Radiation-induced opticneuropathy developed in 32 eyes of 24 patients (9%). The 5-year rates of freedom from RION according to the total dose and once- vs. twice-daily fractionation were as follows: {<=}63 Gy once daily, 95%; {<=}63 Gy twice daily, 98%; >63 Gy once daily, 78%; and >63 Gy twice daily, 91%. Multivariate analysis revealed that the total dose affected the risk of RION (p = 0.0047), with patient age (p = 0.0909), once-daily vs. twice-daily fractionation (p = 0.0684), and overall treatment time (p = 0.0972) were marginally significant. The use of adjuvant chemotherapy did not significantly influence the likelihood of developing RION. Conclusion: The likelihood of developing RION is primarily influenced by the total dose. Hyperfractionation may reduce the risk of experiencing this complication.

Bhandare, Niranjan [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); Monroe, Alan T. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); Morris, Christopher G. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); Bhatti, M. Tariq [Department of Ophthalmology, Neurology, and Neurosurgery, University of Florida College of Medicine, Gainesville, FL (United States); Mendenhall, William M. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States)]. E-mail: mendewil@shands.ufl.edu

To elucidate the cause(s) of acute or subacute bilateral simultaneous opticneuropathy (BSON) in adult life, a follow up study of 23 patients was performed with clinical assessment, brain MRI, HLA typing, and mitochondrial DNA analysis. The results of CSF electrophoresis were available from previous investigations in 11 patients. At follow up, five (22%) had developed clinically definite multiple sclerosis, four (17%) had mitochondrial DNA point mutations indicating a diagnosis of Leber's hereditary opticneuropathy (LHON). The remaining 14 patients (61%) still had clinically isolated BSON a mean of 50 months after the onset of visual symptoms: three of 14 (21%) had multiple MRI white matter lesions compatible with multiple sclerosis, three of 14 (21%) had the multiple sclerosis associated HLA-DR15/DQw6 haplotype, and one of seven tested had CSF oligoclonal IgG bands; in total only five (36%) had one or more of these risk factors. The low frequency of risk factors for the development of multiple sclerosis in these 14 patients suggests that few will develop multiple sclerosis with more prolonged follow up. It is concluded that: (a) about 20% of cases of BSON without affected relatives are due to LHON; (b) multiple sclerosis develops after BSON in at least 20% of cases, but the long term conversion rate is likely to be considerably less than the rate of over 70% seen after an episode of acute unilateral optic neuritis in adult life. PMID:7823072

Purpose. To compare the contrast sensitivity levels of thyroid associated ophthalmopathy (TAO) patients without obvious opticneuropathy with those of healthy people. Methods. Forty eyes of 20 TAO patients without dysthyroid opticneuropathy and 40 eyes of 20 healthy subjects were evaluated in this prospective case-controlled study. The contrast sensitivity functions (CSFs) of all subjects were measured by the functional acuity contrast test (FACT) in five frequencies which were 1,5 cpd (A), 3 cpd (B), 6 cpd (C), 12 cpd (D), and 18 cpd (E). Results were compared for both groups, and a correlation of CSF with Hertel and clinical activity scores was assessed. Results. There was no statistically significant difference between TAO patients and control groups for age and sex. TAO patients had lower levels than the control group in all the frequencies of CSFs (P < 0.05) and the difference in contrast sensitivity functions between the groups seems to be more significant in higher frequencies (B, C, D, and E) (P < 0.001). Conclusions. TAO patients without DON can have contrast sensitivity loss and this would probably imply subtle optic nerve dysfunction in early disease phase. PMID:24453927

NINDS Diabetic Neuropathy Information Page Table of Contents (click to jump to sections) What is Diabetic Neuropathy? Is there any ... Trials Organizations Additional resources from MedlinePlus What is Diabetic Neuropathy? Diabetic neuropathy is a peripheral nerve disorder caused ...

A case report is presented of a 35-year-old woman who developed a progressive right opticneuropathy while surfacing from a series of four recreational dives on the Great Barrier Reef, Queensland, Australia. The patient reported severe sudden onset blurred vision in the right eye associated with a mild headache and epistaxis on surfacing from diving. The patient had her first medical review the day after returning from her trip. At this time visual acuity in the right eye was 20/80, with left eye 20/20. There was a relative afferent pupillary defect in the right eye. A high-resolution computed tomography scan showed fluid in the right sphenoid sinus. Computed perimetry revealed patchy visual field loss in the right eye. The provisional diagnosis of sphenoidal sinus barotrauma-induced opticneuropathy was made. Over 10 days of observation, the visual acuity returned to 20/20 in the right eye and visual field changes resolved. This case highlights a very unusual cause of visual loss associated with diving. PMID:23397871

We report an autosomal recessive neurodegenerative disorder in 25 white members from a large inbred Brazilian family, 22 of whom were evaluated clinically. This condition is characterized by (1) subnormal vision secondary to apparently nonprogressive congenital optic atrophy; (2) onset of progressive spastic paraplegia in infancy; (3) onset of progressive motor and sensory axonal neuropathy in late childhood/early adolescence; (4) dysarthria starting in the third decade of life; (5) exacerbated acoustic startle response; and (6) progressive joint contractures and spine deformities. Motor handicap was severe, and all patients were wheelchair bound after 15 years old. We performed a genome-wide screen including 25 affected individuals and 49 of their unaffected relatives. Linkage was detected at 11q13 region with a maximum logarithm of odds score of +14.43, obtained with marker D11S1883. The candidate region, which lies between D11S1908 and D11S1889, encompasses approximately 4.8Mb and has more than 100 genes and expressed sequences. We propose the acronym SPOAN (spastic paraplegia, optic atrophy, and neuropathy) for this complex syndrome. PMID:15852396

Purpose To define the phenotype and elucidate the molecular basis for an autosomal recessively inherited optic atrophy and auditory neuropathy in a consanguineous family with two affected children. Methods Family members underwent detailed ophthalmologic, electrophysiological, and audiological assessments. An autozygosity mapping strategy using high-density single nucleotide polymorphism microarrays and microsatellite markers was used to detect regions of genome homozygosity that might contain the disease gene. Candidate genes were then screened for mutations by direct sequencing. Results Both affected subjects had poor vision from birth and complained of progressive visual loss over time. Current visual acuity ranged from 6/60 to 6/120. Fundus examination revealed bilateral temporal optic nerve pallor in both patients with otherwise normal retinal findings. International-standard full-field electroretinograms were normal in both individuals, with no evidence of generalized retinal dysfunction. Pattern cortical visual evoked potentials were grossly abnormal bilaterally in both cases. The pattern electroretinogram N95:P50 ratio was subnormal, and the P50 was of shortened peak time bilaterally in both patients. The electrophysiological findings were consistent with bilateral retinal ganglion cell/optic nerve dysfunction. Audiological investigation in both siblings revealed abnormalities falling within the auditory neuropathy/dysynchrony spectrum. There were no auditory symptoms and good outer hair cell function (as demonstrated by transient evoked otoacoustic emissions) but impaired inner hair cell/neural function with abnormal stapedial reflex thresholds and abnormal or absent auditory brainstem-evoked responses. The single nucleotide polymorphism microarray data demonstrated a 24.17 Mb region of homozygosity at 11q14.1–11q22.3, which was confirmed by microsatellite marker analysis. The candidate target region contained the transmembrane protein 126A (TMEM126A) gene, and direct sequencing identified a previously described nonsense mutation (c.163C>T; p.Arg55X). Conclusions We describe the first detailed phenotyping of patients with autosomal recessive TMEM126A-associated optic atrophy and auditory neuropathy. These findings will facilitate the identification of individuals with this recently described disorder. PMID:20405026

Purpose. Geometric morphometrics (GM) was used to analyze the shape of the peripapillary retinal pigment epithelium–Bruch's membrane (RPE/BM) layer imaged on the SD-OCT 5-line raster in normal subjects and in patients with papilledema and ischemic opticneuropathy. Methods. Three groups of subjects were compared: 30 normals, 20 with anterior ischemic opticneuropathy (AION), and 25 with papilledema and intracranial hypertension. Twenty equidistant semilandmarks were digitized on OCT images of the RPE/BM layer spanning 2500 ?m on each side of the neural canal opening (NCO). The data were analyzed using standard GM techniques, including a generalized least-squares Procrustes superimposition, principal component analysis, thin-plate spline (to visualize deformations), and permutation statistical analysis to evaluate differences in shape variables. Results. The RPE/BM layer in normals and AION have a characteristic V shape pointing away from the vitreous; the RPE/BM layer in papilledema has an inverted U shape, skewed nasally inward toward the vitreous. The differences were statistically significant. There was no significant difference in shapes between normals and AION. Pre- and posttreatment OCTs, in select cases of papilledema, showed that the inverted U-shaped RPE/BM moved posteriorly into a normal V shape as the papilledema resolved with weight loss or shunting. Conclusions. The shape difference in papilledema, absent in AION, cannot be explained by disc edema alone. The difference is a consequence of both the translaminar pressure gradient and the material properties of the peripapillary sclera. GM offers a novel way of statistically assessing shape differences of the peripapillary optic nerve head. PMID:21896851

An 81-year-old man presented with poor visual acuity of the left eye, swelling of the left eyelid, and elevation of the left intraocular pressure after contusion of the left palpebral portion. CT revealed left ocular proptosis and left intraorbital hematoma. Traumatic opticneuropathy was suspected, and emergent optic nerve decompression was performed through extradural anterior clinoidectomy followed by optic canal release. Postoperatively, his left visual acuity was markedly improved and the elevated intraocular pressure decreased. Postoperative CT demonstrated improvement of the left ocular proptosis and decompression of the optic nerve. Emergent optic canal release has been recommended in patients who have suffered visual dysfunction caused by optic canal fracture or intraorbital hematoma. The advantages of extradural anterior clinoidectomy followed by optic canal release include a shorter surgical route and easy identification of the optic nerve, resulting in fewer surgical complications. In addition, this procedure can achieve intraorbital decompression. We recommend extradural anterior clinoidectomy followed by optic canal release as a safe and reliable procedure for optic nerve decompression in patients with traumatic opticneuropathy. PMID:25351799

Pedigree analysis of British families with Leber hereditary opticneuropathy (LHON) closely fits a model in which a pathogenic mtDNA mutation interacts with an X-linked visual loss susceptibility locus (VLSL). This model predicts that 60% of affected females will show marked skewing of X inactivation. Linkage analysis in British and Italian families with genetically proven LHON has excluded the presence of such a VLSL over 169 cM of the X chromosome both when all families were analyzed together and when only families with the bp 11778 mutation were studied. Further, there was no excess skewing of X inactivation in affected females. There was no evidence for close linkage to three markers in the pseudoautosomal region of the sex chromosomes. The mechanism of incomplete penetrance and male predominance in LHON remains unclear. 27 refs., 1 fig., 3 tabs.

The authors have investigated the distribution of mutant mtDNA molecules in single cells from a patient with Leber hereditary opticneuropathy (LHON). LHON is a maternally inherited disease that is characterized by a sudden-onset bilateral loss of central vision, which typically occurs in early adulthood. More than 50% of all LHON patients carry an mtDNA mutation at nucleotide position 11778. This nucleotide change converts a highly conserved arginine residue to histidine at codon 340 in the NADH-ubiquinone oxidoreductase subunit 4 (ND4) gene of mtDNA. In the present study, the authors used PCR amplification of mtDNA from lymphocytes to investigate mtDNA heteroplasmy at the single-cell level in a LHON patient. They found that most cells were either homoplasmic normal or homoplasmic mutant at nucleotide position 11778. Some (16%) cells contained both mutant and normal mtDNA.

A frequent occurrence in geriatric and chronically ill patients is the exhibition of several simultaneously occurring and confounding health problems. This paper reports the case of a 61-year-old-white male who presented with an extensive history of multiple brain infarcts, hemiparesis, personality changes and varied visual complaints. Tests in the neurooptometric work-up for this patient included static automated perimetry, stereoacuity and optokinetic nystagmus evaluation. The results were suggestive of multiple cerebrovascular accidents which included the right and left occipital lobes as well as the right parietal lobe. This clinical picture was complicated by the presence of nutritional or ethanol-induced opticneuropathy. Emphasis was placed on a detailed sequential history of events and a complete neurological and optometric evaluation to ascertain the multiple foci of cortical infarction. Corroboration of clinical findings was obtained by computerized axial tomography (CT scan). PMID:1813574

Leber Hereditary OpticNeuropathy (LHON) is an important cause of inherited mitochondrial blindness among young adults. The majority of patients carry one of three mitochondrial DNA (mtDNA) point mutations: m.3460G>A, m.11778G>A and m.14484T>C, all of which affect critical complex I subunits of the mitochondrial respiratory chain. LHON is characterised by marked incomplete penetrance, clearly implying that the mtDNA mutation is insufficient on its own to trigger retinal ganglion cell dysfunction and visual loss. In this case series of three affected patients harbouring the m.11778G>A mutation, we provide evidence suggesting that raised intraocular pressure could be a risk factor triggering visual loss in at-risk LHON carriers. PMID:23667621

Leber's hereditary opticneuropathy (LHON) is a maternally inherited disease associated with point mutations in mitochondrial DNA. The most frequent of these mutations is the G-to-A substitution at nucleotide position 11,778 which changes an evolutionarily conserved arginine with a histidine at position 340 in subunit ND4 of NADH:ubiquinone reductase (respiratory complex I). We report that this amino acid substitution alters the affinity of complex I for the ubiquinone substrate and induces resistance towards its potent inhibitor rotenone in mitochondria of LHON patients. Such changes could reflect a substantial loss in the energy conserving function of NADH:ubiquinone reductase and thus explain the pathological effect of the ND4/11,778 mutation. PMID:7926004

Background Silicone oil endotamponade is used for the repair of complicated retinal detachments. Cataract, glaucoma and corneal endothelial dysfunction are the most frequent complications of silicone oil tamponade. Clinical and histopathological studies have revealed that silicone oil can penetrate into the optic nerve and into the brain. The mechanism by which silicone oil moves from intraocular into the optic nerve is still under debate. To investigate the effect of intraocular pressure only, a post?mortem experimental histological study was performed to determine whether silicone oil penetration from the globe into the optic nerve after vitrectomy and silicone oil instillation is a purely pressure?related phenomenon. Although a post?mortem study excludes physiological processes, it serves as a model for the study of pure physical forces onto biological structures. Methods The study was carried out on 20 human eyes with their optic nerves attached. All specimens had been harvested from patients without known eye disease. The vitreous body was removed with a syringe and the globe was filled with silicone oil. A lipophil fluorescence marker (Bodipy) was added in 8 eyes. The mean intraocular pressure after silicone oil filling measured 40?mm Hg and the globes stayed under pressure for up to 16?weeks. The eyes and optic nerves were stained with H&E and examined with light, phase?contrast and fluorescence microscopy. Results None of the 20 specimens examined showed silicone oil in the retrolaminar portion of the optic nerve. Conclusions Migration of silicone oil into the optic nerve was not demonstrated in this human post?mortem study. Therefore other factors, such as pre?existing glaucomatous damage to the disc region and/or active transport mechanisms must be involved in the development of silicone oil?associated opticneuropathy. PMID:17475700

Optic nerve atrophy caused by abnormal intraocular pressure (IOP) remains the most common cause of irreversible loss of vision worldwide. The aim of this study was to determine whether topically applied IOP-lowering eye drugs affect retinal ganglion cells (RGCs) and retinal metabolism in a rat model of opticneuropathy. IOP was elevated through cauterization of episcleral veins, and then lowered either by the daily topical application of timolol, timolol/travoprost, timolol/dorzolamide, or timolol/brimonidine, or surgically with sectorial iridectomy. RGCs were retrogradely labeled 4 days prior to enucleation, and counted. Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), matrix-assisted laser desorption ionization mass spectrometry, Western blotting, and immunohistochemistry allowed the identification of IOP-dependent proteomic changes. Genomic changes were scrutinized using microarrays and qRT-PCR. The significant increase in IOP induced by episcleral vein cauterization that persisted until 8 weeks of follow-up in control animals (p<0.05) was effectively lowered by the eye drops (p<0.05). As anticipated, the number of RGCs decreased significantly following 8 weeks of elevated IOP (p<0.05), while treatment with combination compounds markedly improved RGC survival (p<0.05). 2D-PAGE and Western blot analyses revealed an IOP-dependent expression of crystallin cry-?b2. Microarray and qRT-PCR analyses verified the results at the mRNA level. IHC demonstrated that crystallins were expressed mainly in the ganglion cell layer. The data suggest that IOP and either topically applied antiglaucomatous drugs influence crystallin expression within the retina. Neuronal crystallins are thus suitable biomarkers for monitoring the progression of neuropathy and evaluating any neuroprotective effects. PMID:23468831

Purpose: To evaluate the intravitreal antivascular endothelial growth factor, bevacizumab, for treatment of radiation opticneuropathy (RON). Methods and Materials: A prospective interventional clinical case series was performed of 14 patients with RON related to plaque radiotherapy for choroidal melanoma. The RON was characterized by optic disc edema, hemorrhages, microangiopathy, and neovascularization. The entry criteria included a subjective or objective loss of vision, coupled with findings of RON. The study subjects received a minimum of two initial injections of intravitreal bevacizumab (1.25 mg in 0.05 mL) every 6-8 weeks. The primary objectives included safety and tolerability. The secondary objectives included the efficacy as measured using the Early Treatment Diabetic Retinopathy Study chart for visual acuity, fundus photography, angiography, and optical coherence tomography/scanning laser ophthalmoscopy. Results: Reductions in optic disc hemorrhage and edema were noted in all patients. The visual acuity was stable or improved in 9 (64%) of the 14 patients. Of the 5 patients who had lost vision, 2 had relatively large posterior tumors, 1 had had the vision decrease because of intraocular hemorrhage, and 1 had developed optic atrophy. The fifth patient who lost vision was noncompliant. No treatment-related ocular or systemic side effects were observed. Conclusions: Intravitreal antivascular endothelial growth factor bevacizumab was tolerated and generally associated with improved vision, reduced papillary hemorrhage, and resolution of optic disc edema. Persistent optic disc neovascularization and fluorescein angiographic leakage were invariably noted. The results of the present study support additional evaluation of antivascular endothelial growth factor medications as treatment of RON.

Aims: To compare the ultrastructural aspects of human extraocular muscles in two types of mitochondrial disease: chronic progressive external ophthalmoplegia (CPEO) and Leber’s hereditary opticneuropathy (LHON).Methods: Muscle samples of the medial rectus obtained from surgery in a sporadic case of CPEO associated with deleted mitochondrial DNA, and post mortem in a case of 3460\\/ND1 LHON were processed for electron

Purpose. To report the serial evaluation of asymptomatic eyes of subjects with mutated G11778A mitochondrial DNA. Methods. Forty-five asymptomatic G11778A Leber hereditary opticneuropathy (LHON) carriers and two patients with the mutation who developed unilateral visual loss underwent testing that included visual acuity, automated visual field, pattern electroretinogram (PERG), and spectral-domain optical coherence tomography every 6 months between September 2008 and March 2012. Results. Visual acuity, visual fields, and retinal nerve fiber layer thickness remained stable within the normal range. Mean PERG amplitudes of carriers dropped progressively by ?40% from baseline to 36 months. In addition, comparisons with the fellow eyes of patients with unilateral optic neuritis revealed a 3.4 ETDRS (Early Treatment Diabetic Retinopathy Study) letter loss in the LHON carriers. A single carrier developed visual loss, with PERG amplitudes dropping by half. In one of two LHON cases who presented with unilateral visual loss, visual acuity in the asymptomatic eye was ?20/40 at baseline. The PERG amplitude of this eye was reduced to ?30% of normal. Six months later, his visual acuity had dropped to ?20/500. A second patient who was ?20/20 and had a visual field defect in the asymptomatic eye at baseline remained at this level for the 18 months of follow-up. His PERG amplitudes were similar to those of asymptomatic carriers, with 0.78 ?V at baseline that did not decline with follow-up. Conclusions. Declines of the PERG amplitude suggest subclinical retinal ganglion cell dysfunction in asymptomatic G11778A subjects, which is progressive. PMID:24398093

Pathogenetic mutations in mtDNA are found in the majority of patients with Leber hereditary opticneuropathy (LHON), and molecular genetic techniques to detect them are important for diagnosis. A false-positive molecular genetic error has adverse consequences for the diagnosis of this maternally inherited disease. The authors found a number of mtDNA polymorphisms that occur adjacent to known LHON-associated mutations and that confound their molecular genetic detection. These transition mutations occur at mtDNA nt 11779 (SfaNI site loss, 11778 mutation), nt 3459 (BsaHI site loss, 3460 mutation), nt 15258 (AccI site loss, 15257 mutation), nt 14485 (mismatch primer Sau3AI site loss, 14484 mutation), and nt 13707 (BstNI site loss, 13708 mutation). Molecular genetic detection of the most common pathogenetic mtDNA mutations in LHON, using a single restriction enzyme, may be confounded by adjacent polymorphisms that occur with a false-positive rate of 2%-7%. 19 refs.

We amplified the 340 bp of mitochondrial DNA (mtDNA) by PCR including the recognized sequence of restriction enzyme of SfaN I. After amplification and digestion of SfaN I, two bands of 190 bp and 150 bp appeared in the mtDNA of four normal individuals but only one band of 340 bp appeared in the mtDNA with the mutation of G to A at the site of the nucleotide 11778 because such mutation destroyed the recognized sequence of SfaN I. We studied the mtDNAs of the patients with Leber's hereditary opticneuropathy from 19 Chinese families and their maternal relatives as well as the normal individuals i. e. the husbands of the female members of the pedigrees. The results show that 66.7% of the patients (30/45) and 54.7% of the maternal relatives (29/53) have such a mutation, while no such a mutation exists in the four normal individuals. So, we conclude that the mutation of mitochondrial DNA at position 11,778 is also a major cause of LHON in China. PMID:7744206

The aim of this study was to determine the incidence of nonarteritic ischemic opticneuropathy (NAION) in the Split-Dalmatia County, Croatia, as part of the Mediterranean region of southern Europe, during a 7-year period (2001-2007). This retrospective study included 87 NAION patients (36 female, median age 68 years, and 51 male, median age 69.5 years) treated at University Department of Ophthalmology, Split University Hospital Center, from January 2001 till December 2007. In each case the diagnosis was confirmed by review of patient records. The annual incidence of NAION was 2.9 per 100,000 (95% CI 1.1-4.8); 3.8 (95% Cl 0.76-6.8) per 100,000 per year in male and 2.5 (95% CI 0.12-4.9) per 100,000 per year in female patients. There was no statistically significant sex difference in the annual incidence of NAION (chi2 = 1.17; P = 0.279). NAION involvement showed a statistically significant male predominance in the > 65 year age group, yielding a relative risk for men vs. women of 1.75. In conclusion, the incidence of NAION in the Split-Dalmatia County was found to be moderate. PMID:19580225

Malabsorptive bariatric surgery is rapidly becoming a major cause of copper deficiency given the increasing prevalence of these procedures for morbid obesity. Acquired copper deficiency can present with clinically significant hematologic and neurological manifestations. Although hematologic manifestations of copper deficiency are rapidly reversible, significant neurological improvement after copper supplementation therapy is unusual and many patients remain debilitated and may only experience, at best, stabilization of the neurological manifestations. Here we present a case of an undiagnosed copper deficiency several years after bariatric gastric bypass surgery, in a patient who concomitantly used zinc-containing denture cream for several years, associated with anemia, neutropenia, myelopathy, respiratory failure, and bilateral opticneuropathy, which caused major vision loss. This patient was also a heterozygote carrier of the 5,10-methylenetetrahydrofolate reductase A1298C gene polymorphism, which may affect copper metabolism. Intravenous copper repletion resulted in rapid correction of hematologic indices. However, neurological manifestations, including vision loss responded only modestly to copper supplementation, despite achieving normal blood copper concentrations. Clinicians should consider copper deficiency in patients at risk, as in this case, as a delayed diagnosis can lead to irreversible disability due to neurological manifestations. PMID:24583748

Objective: To determine whether the association between multiple sclerosis (MS) and Leber hereditary opticneuropathy (LHON) (known as “Harding disease”) is a chance finding, or the 2 disorders are mechanistically linked. Methods: We performed a United Kingdom–wide prospective cohort study of prevalent cases of MS with LHON mitochondrial DNA (mtDNA) mutations. The new cases were compared with published cases, enabling a comprehensive clinical description. We also performed a meta-analysis of studies screening patients with MS for LHON mtDNA mutations to find evidence of a genetic association. Results: Twelve new patients were identified from 11 pedigrees, and 44 cases were identified in the literature. The combined cohort had the following characteristics: multiple episodes of visual loss, predominance for women, and lengthy time interval before the fellow eye is affected (average 1.66 years), which is very atypical of LHON; conversely, most patients presented without eye pain and had a poor visual prognosis, which is unusual for optic neuritis associated with MS. The number of UK cases of LHON-MS fell well within the range predicted by the chance occurrence of MS and the mtDNA mutations known to cause LHON. There was no association between LHON mtDNA mutations and MS in a meta-analysis of the published data. Conclusions: Although the co-occurrence of MS and LHON mtDNA mutations is likely to be due to chance, the resulting disorder has a distinct phenotype, implicating a mechanistic interaction. Patients with LHON-MS have a more aggressive course, and prognostication and treatment should be guarded. PMID:24198293

... are at the highest risk of nerve damage ( diabetic neuropathy ) from diabetes include: Those with damage to the ... A, Ward K. Neuropathic Pain: A Review of Diabetic Neuropathy. US Pharm . 2010;35(5):HS8-HS15.

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Fiber optic distributed sensing systems based on Brillouin scattering are reviewed. Strain or temperature distribution along an optical fiber can be measured with this phenomenon using time domain and correlation domain techniques. Superior functions have already been demonstrated, such as mm order spatial resolution and kHz order measurement speed. Brillouin scattering is accompanied by acoustic grating, which is generated by thermal vibration of fiber material. Recently, considering the nature of the acoustic grating enhanced through stimulated Brillouin scattering process, various advanced functions have been realized in the distributed sensing, such as discriminative measurement of strain and temperature with a 10 cm resolution by a correlation domain technique, realization of cm order resolution by a time domain technique, and distributed birefringence measurement along a polarization maintaining fiber. These Brillouin based systems are also compared briefly with FBG based systems, including distributed sensing with long-length FBG.

In traumatic opticneuropathy (TON), apoptosis of retinal ganglion cells is closely related to the local production of reactive oxygen species and inflammatory mediators from activated microglial cells. Adenosine receptor A2A (A2AAR) has been shown to possess anti-inflammatory properties that have not been studied in TON. In the present study, we examined the role of A2AAR in retinal complications associated with TON. Initial studies in wild-type mice revealed that treatment with the A2AAR agonist resulted in marked decreases in the TON-induced microglial activation, retinal cell death and releases of reactive oxygen species and pro-inflammatory cytokines TNF-? and IL-6. To further assess the role of A2AAR in TON, we studied the effects of A2AAR ablation on the TON-induced retinal abnormalities. A2AAR-/- mice with TON showed a significantly higher mRNA level of TNF-?, Iba1-1 in retinal tissue, and ICAM-1 expression in retinal sections compared with wild-type mice with TON. To explore a potential mechanism by which A2AAR-signaling regulates inflammation in TON, we performed additional studies using hypoxia- or LPS-treated microglial cells as an in vitro model for TON. Activation of A2AAR attenuates hypoxia or LPS-induced TNF-? release and significantly repressed the inflammatory signaling, ERK in the activated microglia. Collectively, this work provides pharmacological and genetic evidence for A2AAR signaling as a control point of cell death in TON and suggests that the retinal protective effect of A2AAR is mediated by attenuating the inflammatory response that occurs in microglia via interaction with MAPKinase pathway. PMID:24090652

Background: The authors investigated the correlation of protan and tritan color vision with disease characteristics in Leber hereditary opticneuropathy (LHON). The authors also characterized the therapeutic potential of idebenone in protecting patients from developing dyschromatopsia in LHON. Methods: Color contrast data of 39 LHON patients participating in a randomized, double-blind placebo-controlled intervention study were evaluated. Patients reported disease onset <5 years before enrolment and were genetically confirmed. Protan and tritan color contrast sensitivity was measured using a computer graphics method in patients receiving idebenone (Catena; 900 mg/d; N = 28) or placebo (N = 11) for 6 months. Results: Mean age of patients was 28.1 years, 87.2% were men, 76.9% carried the m11778G>A mutation, and mean duration since onset was 2 years. Assessing protan and tritan color vision at baseline revealed a high degree of color confusion even in young patients (<25 years) and with a short history of disease (<1 year). Treatment with idebenone improved tritan color vision compared with placebo (P = 0.008 at week 24); a similar trend was seen for protan. The effect of idebenone was most prominent in patients with discordant visual acuity (interocular difference of logMAR >0.2). In this subgroup, the treatment effect at week 24 was 20.4% (P = 0.005) in favor of idebenone for the tritan color domain and 13.5% (P = 0.067) for the protan domain. Conclusion: This study confirms that protan and tritan color confusion is an early symptom in LHON. Treatment with idebenone can protect from loss of color vision, particularly in patients who are at imminent risk of further vision loss. PMID:23263355

Purpose To study mutations associated with Leber hereditary opticneuropathy (LHON) in patients suspected of having this mitochondrial disorder in a Latvian population. Additional aims were to determine the heteroplasmy status of all non-synonymous polymorphisms identified in the current study and to identify the mitochondrial haplogroups of the studied participants because these factors may contribute to the manifestation of LHON. Methods Twelve patients, including patients in two families, were enrolled in the current study. LHON was suspected based on the findings of ophthalmologic examinations. In clinically affected individuals, the presence of all previously reported LHON-associated mutations was assessed with sequencing analysis. Additionally, the SURVEYOR endonuclease assay was used to detect heteroplasmy. The mitochondrial haplogroups were identified with restriction analysis and the sequencing of hypervariable segment 1. Results In one family (mother and son), there was one primary LHON-associated mutation, G11778A. In addition, one rare previously reported LHON-associated polymorphism, A13637G, was detected in two unrelated patients. A non-synonymous polymorphism at T6253C was found in one individual. This mutation was reported in the background of the 3460 mutation among LHON patients in a Chinese population. No non-synonymous point mutations in mitochondrial DNA were found in five of the study participants. Conclusions Molecular analysis of 12 patients with suspected LHON confirmed the diagnosis in four patients and allowed the use of appropriate prophylactic measures and treatment. Further investigations and additional studies of different populations are necessary to confirm the role of the non-synonymous polymorphisms A13637G and T6253C in the manifestation of LHON and the associations of these polymorphisms with mitochondrial haplogroups and heteroplasmy. PMID:24319328

PURPOSE: We conducted extensive epidemiological, neuro-ophthalmological, psychophysical, and blood examinations on a newly discovered, very large pedigree with molecular analysis showing mtDNA mutation for Leber's hereditary opticneuropathy (LHON). METHODS: Four patients representing four index cases from a remote area of Brazil were sent to Sao Paulo, where complete ophthalmological examinations strongly suggested LHON. Molecular analysis of their blood demonstrated that they were LHON, homoplasmic 11778, J-haplogroup. They had an extensive family that all lived in one rural area in Brazil. To investigate this family, we drew on a number of international experts to form a team that traveled to Brazil. This field team also included several members of the Federal University of Sao Paulo, and together we evaluated 273 of the 295 family members that were still alive. We conducted epidemiological interviews emphasizing possible environmental risk factors, comprehensive neuro-ophthalmological examinations, psychophysical tests, Humphrey visual field studies, fundus photography, and blood testing for both mitochondrial genetic analysis and nuclear gene linkage analysis. RESULTS: The person representing the first-generation case immigrated from Verona, Italy, to Colatina. Subsequent generations demonstrated penetrance rates of 71%, 60%, 34%, 15%, and 9%. The percentages of males were 60%, 50%, 64%, 100%, and 100%. Age at onset varied from 10 to 64 years, and current visual acuities varied from LP to 20/400. CONCLUSIONS: Almost 95% of a nearly 300-member pedigree with LHON 11778 were comprehensively studied. Analysis of environmental risk factors and a nuclear modifying factor from this group may help address the perplexing mystery of LHON: Why do only some of the genetically affected individuals manifest the disease? This fully described database may also provide an excellent opportunity for future clinical trials of any purported neuroprotective agent. PMID:12545691

The contrast evoked potentials (VEPs) to different check sizes were recorded in about 200 cases of discrete opticneuropathies (ON) of different origin. Differential light threshold (DLT) was tested with the computer perimeter OCTOPUS. Saturated and desaturated tests were applied to evaluate the degree of acquired color vision deficiency. Delayed VEP responses are not confined to optic neuritis (RBN) alone

A 31-year-old woman developed subacute bilateral visual loss over a 2-week period. Two months later, the diagnosis of Leber hereditary opticneuropathy (LHON) 11778/ND4 was established and the patient was treated with 900 mg of idebenone daily. Over the ensuing 9 months, visual acuity improved from 20/200 to 20/25 in each eye with near-total resolution in visual field abnormalities. Our case report is in agreement with 2 large published series of patients with LHON treated with idebenone, raising hope for treatment of this visually devastating mitochondrial disorder. PMID:22269948

Context: GH excess is a serious complication of McCune-Albright syndrome (MAS) and has been associated with craniofacial morbidity. Objective: The aim of the study was to determine whether early diagnosis and treatment of MAS-associated GH excess prevents opticneuropathy and hearing impairment, the major morbidities associated with GH excess. Design and Setting: A retrospective cross-sectional analysis was conducted at a clinical research center. Patients: Twenty-two subjects with MAS-associated GH excess and 21 control MAS subjects without GH excess were included in the study. Intervention: Biochemical testing included random GH, nadir GH after glucose load, nadir GH on frequent sampling, and IGF-I Z-score. Subjects underwent imaging, ophthalmological, audiological, and otolaryngological assessment. Treatment included octreotide, pegvisomant, transphenoidal surgery, and/or radiotherapy as indicated. Main Outcome Measure: Association of opticneuropathy and hearing impairment to age at GH excess diagnosis/treatment was measured. Results: Of 129 MAS subjects, 26 (20%) were diagnosed with GH excess based on elevation of two measures of GH function. Of these, 22 subjects were candidates for pharmacological intervention. Opticneuropathy was significantly correlated with intervention status, with no cases in the early intervention group (diagnosed/treated before age 18) or the control group, and four of seven (57%) in the late intervention group (diagnosed/treated after age 18) (Fisher's exact test; odds ratio, 0.027; P = 0.0058). Early diagnosis/intervention was not associated with reduction in hearing deficits (odds ratio, 1.25; P = 1.00). Mean head circumference sd score was significantly higher in the late (6.08; range, 2.70 to 22.56) than the early intervention (2.67; range, ?0.65 to 6.72) or control groups (2.13; range, ?2.06 to 7.79) (P = 0.003). Conclusions: Early diagnosis/treatment of GH excess in MAS is important to prevent opticneuropathy and craniofacial expansion. The relationship between hearing deficits and GH excess remains less clear and requires further study. PMID:23093488

Purpose. Scanning laser polarimetry (SLP) reveals abnormal retardance of birefringence in locations of the edematous peripapillary retinal nerve fiber layer (RNFL), which appear thickened by optical coherence tomography (OCT), in nonarteritic anterior ischemic opticneuropathy (NAION). We hypothesize initial sector SLP RNFL abnormalities will correlate with long-term regional visual field loss due to ischemic injury. Methods. We prospectively performed automated perimetry, SLP, and high definition OCT (HD-OCT) of the RNFL in 25 eyes with acute NAION. We grouped visual field threshold and RNFL values into Garway-Heath inferior/superior disc sectors and corresponding superior/inferior field regions. We compared sector SLP RNFL thickness with corresponding visual field values at presentation and at >3 months. Results. At presentation, 12 eyes had superior sector SLP reduction, 11 of which had inferior field loss. Six eyes, all with superior field loss, had inferior sector SLP reduction. No eyes had reduced OCT-derived RNFL acutely. Eyes with abnormal field regions had corresponding SLP sectors thinner (P = 0.003) than for sectors with normal field regions. During the acute phase, the SLP-derived sector correlated with presentation (r = 0.59, P = 0.02) and with >3-month after presentation (r = 0.44, P = 0.02) corresponding superior and inferior field thresholds. Conclusions. Abnormal RNFL birefringence occurs in sectors corresponding to regional visual field loss during acute NAION when OCT-derived RNFL shows thickening. Since the visual field deficits show no significant recovery, SLP can be an early marker for axonal injury, which may be used to assess recovery potential at RNFL locations with respect to new treatments for acute NAION. PMID:23838768

Purpose The clinical impact of mDNA mutations on the development of Leber hereditary opticneuropathy (LHON) may be modulated by mitochondrial haplogroups, which vary across populations. The aim of this research was to determine the clinical spectrum and molecular characteristics, including the haplogroup, of 15 South American families with LHON. Methods This study was a prospective, observational study conducted between March 2006 and August 2012. All patients were referred to the Clinical Hospital of the University of Chile, where the clinical study was conducted. Molecular studies were conducted at the Biomedical Sciences Institute (ICBM) of the University of Chile. Fifteen index cases were identified with molecular analysis after initial neuroophthalmic examination at different centers throughout Chile. Clinical features of patients with LHON and maternal relatives of the 15 families (75 individuals: 26 affected and 49 healthy carriers) were evaluated. The primary mDNA mutations (m.3460G>A, m.11778G>A, or m.14484T>C) were determined with restriction fragment length polymorphism analysis in all individuals. Mitochondrial haplogroups were determined with direct sequencing of two hypervariable regions (HV1 and HV2) and compared with reference sequences. Results The m.11778G>A mutation was found in 59 subjects (78.7%), the m.14484T>C mutation was found in 12 subjects (16.0%), and the m.3460G>A mutation was found in four (5.3%) subjects. The average age of onset of symptoms in affected subjects was 22.2 years old (range 3 to 53 years); 21 (80.7%) were male, and five (19.3%) were female. Twelve families (80%) had Amerindian haplogroups: One family had the A2 haplogroup, four families had the B2i2 haplogroup, six families had the C1b haplogroup, and one family had the D1g haplogroup. Conclusions In this limited sample size, the Amerindian haplogroup A2 was associated with delayed onset of disease in this population. Patients with haplogroup C retained better vision than the patients with other haplogroups in this population. Disease in subjects with haplogroup D appeared to be underrepresented compared to the population at large. PMID:24672219

Peripheral neuropathy can be caused by medication, and various descriptions have been applied for this condition. In this MiniReview, the term 'drug-induced peripheral neuropathy' (DIPN) is used with the suggested definition: Damage to nerves of the peripheral nervous system caused by a chemical substance used in the treatment, cure, prevention or diagnosis of a disease. Opticneuropathy is included in this definition. A distinction between DIPN and other aetiologies of peripheral neuropathy is often quite difficult and thus, the aim of this MiniReview is to discuss the major agents associated with DIPN. PMID:24786912

Polyneuropathy is one of the commonest complications of the diabetes and the commonest form of neuropathy in the developed\\u000a world. Diabetic polyneuropathy encompasses several neuropathic syndromes, the most common of which is distal symmetrical neuropathy,\\u000a the main initiating factor for foot ulceration. The epidemiology of diabetic neuropathy has recently been reviewed in reasonable\\u000a detail (1). Several clinic- (2,3) and populationbased

Opinion statement Inherited peripheral neuropathies are among the most common hereditary diseases of the nervous system. Charcot-Marie-Tooth\\u000a (CMT) disease, also known from previous classifications as hereditary motor and sensory neuropathy (HMSN), is certainly the\\u000a most common inherited neuropathy. In the past several years, various treatments for CMT have been proposed, although specific\\u000a therapies are not yet available. In clinical practice, rehabilitative

Leber hereditary opticneuropathy (LHON) is maternally transmitted and is characterized by bilateral loss of central vision in young adults as a result of optic nerve degeneration. Fifteen transition mutations located in different genes for the mitochondrially encoded subunits of respiratory chain complexes have been associated thus far with the disease. Genetic studies have led to the classification of the pathogenic significance of these different mutations. However, more research is required to determine the causality of the mutations and the penetrance of the disease. The present study compares studies of populations of different ethnic origins, namely European LHON pedigrees and sporadic cases, in order to elucidate the pathogenic mechanisms involved. 21 refs., 2 figs., 1 tab.

Non-arteritic anterior ischemic opticneuropathy (NA-AION) is the most common cause of acute ischemic damage to the optic nerve (ON), and the leading cause of seriously impaired vision in people over 55 years of age. It demonstrated that subcutaneous administration of Granulocyte colony-stimulating factor (G-CSF) reduces RGC death in an ON crush model in rats, and that the neuroprotective effects may involve both anti-apoptotic and anti-inflammatory processes. Our recent work shows that the protective actions of G-CSF in rAION models may involve both anti-apoptotic and anti-inflammatory processes. However, the exact rescuing mechanisms involved in the administration of G-CSF in rAION models need further investigation. In addition, further studies on the administration of G-CSF at different time intervals after the induction of rAION may be able to illustrate whether treatment given at a later time is still neuroprotective. Further, it is unknown whether treatment using G-CSF combined with other drugs will result in a synergistic effect in a rAION model. Inflammation induced by ischemia plays an essential role on the ON head in NA-AION, which can result in disc edema and compartment changes. Therefore, it is reasonable that adding an anti-inflammatory drug may enhance the therapeutic effects of G-CSF. An ongoing goal is to evaluate the novel sites of action of both G-CSF and other anti-inflammatory drugs, and to identify the functionally protective pathways to enhance RGC survival. These investigations may open up new therapeutic avenues for the treatment of ischemic opticneuropathy.

The Tas2 and Vic2 Australian families are affected with a variant of Leber hereditary opticneuropathy (LHON). The risk of developing the opticneuropathy shows strict maternal inheritance, and the opthalmological changes in affected family members are characteristic of LHON. However, in contrast to the common form of the disease, members of these two families show a high frequency of vision recovery. To ascertain the mitochondrial genetic etiology of the LHON in these families, both (a) the nucleotide sequences of the seven mitochondrial genes encoding subunits of respiratory-chain complex I and (b) the mitochondrial cytochrome b gene were determined for representatives of both families. Neither family carries any of the previously identified primary mitochondrial LHON mutations: ND4/11778, ND1/3460, or ND1/4160. Instead, both LHON families carry multiple nucleotide changes in the mitochondrial complex I genes, which produce conservative amino acid changes. From the available sequence data, it is inferred that the Vic2 and Tas2 LHON families are phylogenetically related to each other and to a cluster of LHON families in which mutations in the mitochondrial cytochrome b gene have been hypothesized to play a primary etiological role. However, sequencing analysis establishes that the Vic2 and Tas2 LHON families do not carry these cytochrome b mutations. There are two hypotheses to account for the unusual mitochondrial genetic etiology of the LHON in the Tas2 and Vic2 LHON families. One possibility is that there is a primary LHON mutation within the mitochondrial genome but that it is at a site that was not included in the sequencing analyses. Alternatively, the disease in these families may result from the cumulative effects of multiple secondary LHON mutations that have less severe phenotypic consequences. 29 refs., 3 figs., 3 tabs.

A limited autonomic neuropathy may underlie some unusual clinical syndromes, including the postural tachycardia syndrome, pseudo-obstruction syndrome, heat intolerance, and perhaps chronic fatigue syndrome. Antibodies to autonomic structures are common in diabetes, but their specificity is unknown. The presence of autonomic failure worsens prognosis in the diabetic state. Some autonomic neuropathies are treatable. Familial amyloid polyneuropathy may respond to liver transplantation. There are anecdotal reports of acute panautonomic neuropathy responding to intravenous gamma globulin. Orthostatic hypotension may respond to erythropoietin or midodrine.

We propose and demonstrate an all-optical XOR logic gate accompanied with modulation format conversion from non-return-to-zero on-off-keying to return-to-zero binary phase-shift-keying by the use of cross-phase modulation in optical fiber.

... and chronic forms can exhibit a pattern of alternating remission and relapse. Acute inflammatory demyelinating neuropathy, better known as Guillain-Barré syndrome, can damage motor, sensory, and autonomic nerve fibers. Most people recover ...

... this condition. In severe cases, nerves that regulate internal body functions (autonomic nerves) may be involved. Risks of alcoholic neuropathy include: Long-term, heavy alcohol use Alcoholism that is present for 10 years or more

Purpose. Nonarteritic anterior ischemic opticneuropathy (NAION) is the most common cause of sudden optic nerve–related vision loss in persons older than 50 in the United States. There currently is no treatment for this disorder. We previously showed that systemic administration of 15-deoxy, delta (12, 14) prostaglandin J2 (PGJ2) is neuroprotective in our rodent model of AION (rAION). In this study, we determined if a single intravitreal (IVT) injection of PGJ2 is neuroprotective after rAION, and if this method of administration is toxic to the retina, optic nerve, or both. Methods. Toxicity was assessed after a single IVT injection of PGJ2 in one eye and PBS in the contralateral eye of normal, adult Long-Evans rats. Efficacy was assessed by inducing rAION in one eye and injecting either PGJ2 or vehicle immediately following induction, with the fellow eye serving as naïve control. Visual evoked potentials (VEPs) and ERGs were performed before induction and at specific intervals thereafter. Animals were euthanized 30 days after induction, after which immunohistochemistry, transmission electron microscopy, and quantitative stereology of retinal ganglion cell (RGC) numbers were performed. Results. Toxicity: IVT PGJ2 did not alter the VEP or ERG compared with PBS-injected control eyes, and neither IVT PGJ2 nor PBS reduced overall RGC numbers. Efficacy: IVT PGJ2 preserved VEP amplitude, reduced optic nerve edema, and resulted in significant preservation of RGCs and axons in eyes with rAION. Conclusions. A single IVT injection of PGJ2 is nontoxic to the retina and optic nerve and neuroprotective when given immediately after rAION induction. PMID:24106118

We compared the pupil responses originating from outer versus inner retinal photoreception between patients with isolated hereditary opticneuropathy (HON, n = 8) and healthy controls (n = 8). Three different testing protocols were used. For the first two protocols, a response function of the maximal pupil contraction versus stimulus light intensity was generated and the intensity at which half of the maximal pupil contraction, the half-max intensity, was determined. For the third protocol, the pupil size after light offset, the re-dilation rate and re-dilation amplitude were calculated to assess the post-light stimulus response. Patients with HON had bilateral, symmetric optic atrophy and significant reduction of visual acuity and visual field compared to controls. There were no significant mean differences in the response curve and pupil response parameters that reflect mainly rod, cone or melanopsin activity between patients and controls. In patients, there was a significant correlation between the half-max intensity of the red light sequence and visual field loss. In conclusion, pupil responses derived from outer or inner retinal photoreception in HON patients having mild-to moderate visual dysfunction are not quantitatively different from age-matched controls. However, an association between the degree of visual field loss and the half-max intensity of the cone response suggests that more advanced stages of disease may lead to impaired pupil light reflexes. PMID:24275502

Leber's hereditary opticneuropathy (LHON) is an inherited disease caused by mutations in complex I of the mitochondrial respiratory chain. The disease is characterized by loss of central vision due to retinal ganglion cell (RGC) dysfunction and optic nerve atrophy. Despite progress towards a better understanding of the disease, no therapeutic treatment is currently approved for this devastating disease. Idebenone, a short-chain benzoquinone, has shown promising evidence of efficacy in protecting vision loss and in accelerating recovery of visual acuity in patients with LHON. It was therefore of interest to study suitable LHON models in vitro and in vivo to identify anatomical correlates for this protective activity. At nanomolar concentrations, idebenone protected the rodent RGC cell line RGC-5 against complex I dysfunction in vitro. Consistent with the reported dosing and observed effects in LHON patients, we describe that in mice, idebenone penetrated into the eye at concentrations equivalent to those which protected RGC-5 cells from complex I dysfunction in vitro. Consequently, we next investigated the protective effect of idebenone in a mouse model of LHON, whereby mitochondrial complex I dysfunction was caused by exposure to rotenone. In this model, idebenone protected against the loss of retinal ganglion cells, reduction in retinal thickness and gliosis. Furthermore, consistent with this protection of retinal integrity, idebenone restored the functional loss of vision in this disease model. These results support the pharmacological activity of idebenone and indicate that idebenone holds potential as an effective treatment for vision loss in LHON patients. PMID:23028832

Leber hereditary opticneuropathy (LHON) is a mitochondrially inherited form of visual dysfunction caused by mutations in several genes encoding subunits of the mitochondrial respiratory NADH-ubiquinone oxidoreductase complex (complex I). Development of gene therapies for LHON has been impeded by genetic heterogeneity and the need to deliver therapies to the mitochondria of retinal ganglion cells (RGCs), the cells primarily affected in LHON. The therapy under development entails intraocular injection of a nuclear yeast gene NADH-quinone oxidoreductase (NDI1) that encodes a single subunit complex I equivalent and as such is mutation independent. NDI1 is imported into mitochondria due to an endogenous mitochondrial localisation signal. Intravitreal injection represents a clinically relevant route of delivery to RGCs not previously used for NDI1. In this study, recombinant adenoassociated virus (AAV) serotype 2 expressing NDI1 (AAV-NDI1) was shown to protect RGCs in a rotenone-induced murine model of LHON. AAV-NDI1 significantly reduced RGC death by 1.5-fold and optic nerve atrophy by 1.4-fold. This led to a significant preservation of retinal function as assessed by manganese enhanced magnetic resonance imaging and optokinetic responses. Intraocular injection of AAV-NDI1 overcomes many barriers previously associated with developing therapies for LHON and holds great therapeutic promise for a mitochondrial disorder for which there are no effective therapies. PMID:22669418

BACKGROUND\\/AIMSHyperhomocyst(e)inaemia has been identified as a strong risk factor for stroke, myocardial infarction, and deep vein thrombosis. A point mutation of methylene tetrahydrofolate reductase (MTHFR C677T) has been associated with increased plasma homocyst(e)ine levels. To investigate whether hyperhomocyst(e)inaemia and\\/or MTHFR C677T mutation are associated with non-arteritic ischaemic opticneuropathy (NAION), a case-control study including 59 consecutive patients with NAION and

Between about 1955 and 1970, some 100,000 Japanese were diagnosed as having subacute myelooptic neuropathy (SMON), a new disease characterized by abdominal and neurological manifestations, the former nearly always preceding the latter. Circumstantial evidence obtained in 1969-70 suggested that SMON might have been caused by clioquinol (CQL), a gastrointestinal disinfectant, and led to the suspension of further sales of CQL in Japan. However, several inconsistencies for the CQL theory of SMON have now emerged; first, CQL had been widely used in Japan for nearly 20 years before SMON occurred. Secondly, the SMON epidemic began to subside several months before CQL sales were suspended. Thirdly, a large proportion of SMON patients--probably about one-third and possibly more--had not taken CQL within six months of the onset of the disease (the modal interval between first taking CQL and the onset of SMON being about three weeks, and more than 100 days in only 4% of SMON patients); of the remaining two-thirds or so, many had taken CQL as part of the treatment of the first (that is, abdominal) symptoms of SMON itself. Fourthly, there was no dose-response relationship. Finally, SMON rarely, if ever, occurred outside Japan. CQL could, however, have been involved in the causation of SMON as an optional enhancer of some other necessary cause; the history of post-war environmental pollution in Japan is compatible with this hypothesis. Over-readiness to accept postulated toxic effects of medicines and chemicals as proven is likely to do at least as much harm as good to individual and community health. PMID:127638

A rare form of Leber hereditary opticneuropathy (LHON) that is associated with hereditary spastic dystonia has been studied in a large Dutch family. Neuropathy and ophthalmological lesions were present together in some family members, whereas only one type of abnormality was found in others. mtDNA mutations previously reported in LHON were not present. Sequence analysis of the protein-coding mitochondrial genes revealed two previously unreported mtDNA mutations. A heteroplasmic A{yields}G transition at nucleotide position 11696 in the ND4 gene resulted in the substitution of an isoleucine for valine at amino acid position 312. A second mutation, a homoplasmic T{yields}A transition at nucleotide position 14596 in the ND6 gene, resulted in the substitution of a methionine for the isoleucine at amino acid residue 26. Biochemical analysis of a muscle biopsy revealed a severe complex I deficiency, providing a link between these unique mtDNA mutations and this rare, complex phenotype including Leber opticneuropathy. 80 refs., 2 figs., 3 tabs.

A rare form of Leber hereditary opticneuropathy (LHON) that is associated with hereditary spastic dystonia has been studied in a large Dutch family. Neuropathy and ophthalmological lesions were present together in some family members, whereas only one type of abnormality was found in others. mtDNA mutations previously reported in LHON were not present. Sequence analysis of the protein-coding mitochondrial genes revealed two previously unreported mtDNA mutations. A heteroplasmic A-->G transition at nucleotide position 11696 in the ND4 gene resulted in the substitution of an isoleucine for valine at amino acid position 312. A second mutation, a homoplasmic T-->A transition at nucleotide position 14596 in the ND6 gene, resulted in the substitution of a methionine for the isoleucine at amino acid residue 26. Biochemical analysis of a muscle biopsy revealed a severe complex I deficiency, providing a link between these unique mtDNA mutations and this rare, complex phenotype including Leber opticneuropathy. PMID:8644732

Background Specific cross-reacting autoimmunity against recoverin or collapsin response mediator protein (CRMP)-5 is known to cause cancer-associated retinopathy or paraneoplastic opticneuropathy, respectively. We report a rare case with small cell lung carcinoma developing bilateral neuroretinitis and unilateral focal outer retinitis positive for these antibodies. Case presentation A 67-year-old man developed bilateral neuroretinitis and foveal exudation in the right eye. Optical coherence tomography showed a dome-shaped hyperreflective lesion extending from inner nuclear layer to the photoreceptor layer at the fovea in the right eye. Single-flash electroretinography showed normal a-waves in both eyes and slightly reduced b-wave in the left eye. Results of serological screening tests for infection were within normal limits. The patient’s optic disc swelling and macular exudation rapidly improved after oral administration of prednisolone. Systemic screening detected lung small cell carcinoma and systemic chemotherapy was initiated. Immunoblot analyses using the patient’s serum detected autoantibodies against recoverin, CRMP-5, and ?-enolase, but not carbonic anhydrase II. Neuroretinitis once resolved after almost remission of carcinoma on imaging but it recurred following the recurrence of carcinoma. Conclusions The development of neuroretinitis in this cancer patient with anti-retinal and anti-optic nerve antibodies depended largely on the cancer activity, suggesting the possible involvement of paraneoplastic mechanisms. Patients with paraneoplastic opticneuropathy and retinopathy are likely to develop autoimmune responses against several antigens, thus leading to various ophthalmic involvements. PMID:24428923

Wolfram syndrome (WFS) is a degenerative disease with neurological and endocrine disorders, characterized by the association of juvenile diabetes mellitus and bilateral optic atrophy. A polyneuropathy was exceptionally described but its characteristics are not well-established. In addition to our observation, we searched all case reports of patients with WFS in the medical literature (more than 600), and selected patients who underwent an EMG: twenty-one patients underwent an EMG, which was considered as abnormal in only 8 cases. The common profile was axonal sensory-motor polyneuropathy, sometimes with marked decrease of motor conduction velocities. This neuropathy could be due to diabetes mellitus, even though microangiopathic and macroangiopathic complications are rare in WFS. Another origin for this neuropathy could be a degenerative process in relationship with WFS. PMID:20888932

Nucleotide-sequencing and multiplexed primer-extension assays have been used to quantitate the mutant-allele frequency in 14 maternal relatives, spanning three generations, from a family that is heteroplasmic for the primary Leber hereditary opticneuropathy (LHON) mutation at nucleotide 3460 of the mitochondrial genome. There was excellent agreement between the values that were obtained with the two different methods. The longitudinal study shows that the mutant-allele frequency was constant within individual family members over a sampling period of 3.5 years. Second, although there was an overall increase in the mutant-allele frequency in successive generations, segregation in the direction of the mutant allele was not invariant, and there was one instance in which there was a significant decrease in the frequency from parent to offspring. From these two sets of results, and from previous studies of heteroplasmic LHON families, we conclude that there is no evidence for a marked selective pressure that determines the replication, segregation, or transmission of primary LHON mutations to white blood cells and platelets. Instead, the mtDNA molecules are most likely to replicate and segregate under conditions of random drift at the cellular level. Finally, the pattern of transmission in this maternal lineage is compatible with a developmental bottleneck model in which the number of mitochondrial units of segregation in the female germ line is relatively small in relation to the number of mtDNA molecules within a cell. However, this is not an invariant pattern for humans, and simple models of mitochondrial gene transmission are inappropriate at the present time. 37 refs., 4 figs., 1 tab.

Pressure-related vision loss has been reported during ascent to altitude. We report the case of an otherwise healthy diver who suffered painless, sudden-onset binocular vision loss at depth, followed by complete recovery immediately upon surfacing. We examine the dive and briefly discuss the differential diagnosis of transient vision loss in the setting of ambient pressure changes. We conclude that the diver likely suffered from sphenoid sinus barotrauma, possibly in association with dehiscence of the bony canals of the optic nerves as they travel in close proximity to the walls of the sphenoid sinus. PMID:23045919

The m.14484T>C mutation in mitochondrial ND6 gene (MT-ND6) is a primary mutation underlying the development of Leber's hereditary opticneuropathy (LHON) , but by itself not enough to cause visual loss. To explore the role of mitochondrial haplogroups on the expression of LHON for the people carrying the m.14484T>C mutation, we performed systematic and extended mutational screening of MT-ND6 gene in a cohort of 1177 Han Chinese patients with LHON. A total of 67 affected subjects carried the homoplasmic m.14484T>C mutation, accounting for 5.7% of this LHON population. The penetrances of opticneuropathy among 51 pedigrees carrying the m.14484T>C mutation ranged from 5.6% to 100.0%, with the average of 21.5%. The sequence analysis of entire mitochondrial genomes of 51 probands exhibited distinct sets of polymorphisms belonging to 18 Eastern Asian haplogroups. The frequencies of haplogroup A and haplogroup F were sig-nificantly less in the LHON mtDNA samples than those in 106 Chinese controls. On the other hand, the haplogroup M10a accounted for 9.8% of the patient's mtDNA samples but was absent in 106 Chinese controls. Strikingly, the average pene-trance (46.13%) of opticneuropathy for the pedigrees carrying mitochondrial haplogroup M10a was higher than those car-rying other mtDNA haplogroups. These observations indicated that mitochondrial haplogroup M10a may increase the risk of visual loss. PMID:24846978

A variation in the properties of indium-tin-oxide (ITO) films obtained by the method of reactive magnetron sputtering with simultaneous ion treatment is reported. The ITO films feature the following parameters in the optical range of 450-1100 nm: a transmission coefficient of 80%, band gap of 3.50-3.60 eV, and a refractive index of 1.97-2.06. All characteristics of the films depend on the ion-treatment current. The latter, during the course of deposition, reduces the resistivity of the ITO films with the smallest value of the resistivity being equal to 2 Multiplication-Sign 10{sup -3} {Omega} cm. The degradation of films with a high resistivity when kept in air is observed.

OBJECTIVE: To evaluate the clinical, electrophysiologic, autonomic, and neuropathologic characteristics and the natural history of subacute diabetic proximal neuropathy and its response to immunotherapy. MATERIAL AND METHODS: For the 12-year period from 1983 to 1995, we conducted a retrospective review of medical records of Mayo Clinic patients with diabetes who had subacute onset and progression of proximal weakness. The responses of treated versus untreated patients were compared statistically. RESULTS: During the designated study period, 44 patients with subacute diabetic proximal neuropathy were encountered. Most patients were middle-aged or elderly, and no sex preponderance was noted. The proximal muscle weakness often was associated with reduced or absent lower extremity reflexes. Associated weight loss was a common finding. Frequently, patients had some evidence of demyelination on nerve conduction studies, but it invariably was accompanied by concomitant axonal degeneration. The cerebrospinal fluid protein concentration was usually increased. Diffuse and substantial autonomic failure was generally present. In most cases, a sural nerve biopsy specimen suggested demyelination, although evidence of an inflammatory infiltrate was less common. Of 12 patients who received treatment (with prednisone, intravenous immune globulin, or plasma exchange), 9 had improvement of their conditions, but 17 of 29 untreated patients (59%) with follow-up also eventually had improvement, albeit at a much slower rate. Improvement was usually incomplete. CONCLUSION: We suggest that the entity of subacute diabetic proximal neuropathy is an extensive and severe variant of bilateral lumbosacral radiculoplexopathy, with some features suggestive of an immune-mediated cause. It differs from chronic inflammatory demyelinating polyradiculoneuropathy in that most cases have a more restricted distribution and seem to be monophasic and self-limiting. The efficacy of immunotherapy is unproved, but such intervention may be considered in the severe and progressive cases or ones associated with severe neuropathic pain.

Three mtDNA point mutations at nucleotide position (np) 3460, at np 11778 and at np 14484, are thought to be of primary importance in the pathogenesis of Leber hereditary opticneuropathy (LHON), a maternally inherited disease characterized by subacute central vision loss. These mutations are present in genes coding for subunits of complex I (NADH dehydrogenase) of the respiratory chain, occur exclusively in LHON maternal pedigrees, and have never been reported to occur together. Johns and Neufeld postulated that an mtDNA mutation at np 9438, in the gene coding for one of the subunits (COX III) of complex IV (cytochrome c oxidase), was also of primary importance. Johns and Neufeld (1993) found this mutation, which changed a conserved glycine to a serine, in 5 unrelated LHON probands who did not carry one of the presently known primary mutations, but they did not find it in 400 controls. However, the role of this sequence variant has been questioned in the Journal when it has been found to occur in apparently healthy African and Cuban individuals. Subsequently, Johns et al. described this mutation in two Cuban individuals presenting with optic and peripheral neuropathy. 22 refs., 1 fig., 1 tab.

Purpose: To assess the incident rates of vision loss (VL; based on counting fingers or more severe) caused by radiation-induced opticneuropathy (RION) after particle therapy for tumors adjacent to optic nerves (ONs), and to evaluate factors that may contribute to VL. Methods and Materials: From August 2001 to August 2006, 104 patients with head-and-neck or skull-base tumors adjacent to ONs were treated with carbon ion or proton radiotherapy. Among them, 145 ONs of 75 patients were irradiated and followed for greater than 12 months. The incident rate of VL and the prognostic factors for occurrence of VL were evaluated. The late effects of carbon ion and proton beams were compared on the basis of a biologically effective dose at alpha/beta = 3 gray equivalent (GyE{sub 3}). Results: Eight patients (11%) experienced VL resulting from RION. The onset of VL ranged from 17 to 58 months. The median follow-up was 25 months. No significant difference was observed between the carbon ion and proton beam treatment groups. On univariate analysis, age (>60 years), diabetes mellitus, and maximum dose to the ON (>110 GyE{sub 3}) were significant, whereas on multivariate analysis only diabetes mellitus was found to be significant for VL. Conclusions: The time to the onset of VL was highly variable. There was no statistically significant difference between carbon ion and proton beam treatments over the follow-up period. Based on multivariate analysis, diabetes mellitus correlated with the occurrence of VL. A larger study with longer follow-up is warranted.

Background To assess the sensitivity and specificity of hemifield pattern electroretinogram (HF-PERG) for detecting early retinal ganglion cell (RGC) damage in ocular hypertensive (OH) patients. Methods Fifty-two OH patients (mean age 56±9.6 years) with an intraocular pressure (IOP) .21 mmHg were assessed. All subjects underwent HF-PERG, optical coherence tomography (OCT), and frequency doubling technology (FDT) visual field. Results OH patients showed a significant increase of peak-time of the N95 (P=0.027) compared to controls. The amplitude of the N95 of the lower and upper HF-PERG showed significant differences (P=0.037 and P=0.023, respectively) between the two groups. A significant intraocular (P=0.006) and interocular (P=0.018) asymmetry of N95 amplitude was found. Receiver operating characteristic (ROC) curve analysis revealed a sensitivity of 93% for the N95 of the lower HF-PERG, whereas full-field pattern electroretinogram (PERG) N95 peak-time had a sensitivity of 88%. In OH patients, we found a thinning of OCT - retinal nerve fiber layer (RNFL), especially in the superior and inferior quadrant, although not statistically significant, and a significantly higher FDT pattern standard deviation (FDT-PSD; P=0.001). In the OCT-RNFL inferior quadrant, a sensitivity of 82% was recorded. Finally, the sensitivity of the FDT-PSD was 92%. Conclusion Our study shows that HF-PERG is a very sensitive test for detecting early damage of the RGC. PMID:25284979

Neuropathy secondary to drugs is a loss of sensation or movement in a part of the body ... weakness. Many medications may affect the development of neuropathy, including: Heart or blood pressure medications Amiodarone Hydralazine ...

Two patients with congenital hypomyelinating neuropathy are reported with details of sural nerve pathology. The resemblance of this condition to the hypomyelinating neuropathy of Trembler mice is discussed and the pertinent medical literature reviewed. Images PMID:4087003

Leber hereditary opticneuropathy (LHON) is associated with mutations of mtDNA, but two features of LHON pedigrees are not explicable solely on the basis of mitochondrial inheritance. There is a large excess of affected males, and not all males at risk develop the disease. These observations could be explained by the existence of an X-linked visual loss susceptibility gene. This hypothesis was supported by linkage studies in Finland, placing the susceptibility locus at DXS7, with a maximum lod score of 2.48 at a recombination fraction of 0. Linkage studies in 1 Italian and 12 British families with LHON, analyzed either together or separately depending on the associated mtDNA mutation, have excluded the presence of such a locus from an interval of about 30 cM around DXS7 in these kindreds, with a total lod score of -26.51 at a recombination fraction of 0. 17 refs., 2 figs., 1 tab.

Abstract Many incurable mitochondrial disorders result from mutant mitochondrial DNA (mtDNA) and impaired respiration. Leigh's syndrome (LS) is a fatal neurodegenerative disorder of infants, and Leber's hereditary opticneuropathy (LHON) causes blindness in young adults. Treatment of LHON and LS cells harboring G11778A and T8993G mutant mtDNA, respectively, by >90%, with healthy donor mtDNA complexed with recombinant human mitochondrial transcription factor A (rhTFAM), improved mitochondrial respiration by ?1.2-fold in LHON cells and restored >50% ATP synthase function in LS cells. Mitochondrial replication, transcription, and translation of key respiratory genes and proteins were increased in the short term. Increased NRF1, TFAMB1, and TFAMA expression alluded to the activation of mitochondrial biogenesis as a mechanism for improving mitochondrial respiration. These results represent the development of a therapeutic approach for LHON and LS patients in the near future. PMID:22390282

A G-to-A transition at nucleotide pair (np) 7444 in the mtDNA was found to correlate with Leber hereditary opticneuropathy (LHON). The mutation eliminates the termination codon of the cytochrome c oxidase subunit I (COI) gene, extending the COI polypeptide by three amino acids. The mutation was discovered as an XbaI restriction-endonuclease-site loss present in 2 (9.1%) of 22 LHON patients who lacked the np 11778 LHON mutation and in 6 (1.1%) of 545 unaffected controls. The mutant polypeptide has an altered mobility on SDS-PAGE, suggesting a structural alteration, and the cytochrome c oxidase enzyme activity of patient lymphocytes is reduced approximately 40% relative to that in controls. These data suggest that the np 7444 mutation results in partial respiratory deficiency and thus contributes to the onset of LHON. Images Figure 1 Figure 3 PMID:1322638

The authors present results and experience in sixteen specific disciplines related to the study of nerve physiopathology, diagnosis and treatment. Twenty-two different peripheral neuropathies are presented, and different models related to health care strategies are discussed. The authors report on Inflammatory and autoimmune neuropathies and Genetic neuropathies.

Inherited neuropathies are caused by dominant or recessive mutations in genes that are expressed by neurons and\\/or Schwann cells. In demyelinating neuropathies, the deleterious effects originate primarily in myelinating Schwann cells. In axonal neuropathies, neurons (axons) are initially affected. In demyelinating neuropathies, the axonal cytoskeleton is altered and axonal transport is disrupted. In some axonal neuropathies, genes that are directly

Primary mitochondrial disorders occur at a prevalence of one in 10?000; ?50% of these demonstrate ocular pathology. Leber hereditary opticneuropathy (LHON) is the most common primary mitochondrial disorder. LHON results from retinal ganglion cell pathology, which leads to optic nerve degeneration and blindness. Over 95% of cases result from one of the three common mutations in mitochondrial genes MTND1, MTND4 and MTND6, which encode elements of the complex I respiratory chain. Various therapies for LHON are in development, for example, intravitreal injection of adeno-associated virus carrying either the yeast NDI1 gene or a specific subunit of mammalian Complex I have shown visual improvement in animal models. Given the course of LHON, it is likely that in many cases prompt administration may be necessary before widespread cell death. An alternative approach for therapy may be the use of stem cells to protect visual function; this has been evaluated by us in a rotenone-induced model of LHON. Freshly dissected embryonic retinal cells do not integrate into the ganglion cell layer (GCL), unlike similarly obtained photoreceptor precursors. However, cultured retinal progenitor cells can integrate in close proximity to the GCL, and act to preserve retinal function as assessed by manganese-enhanced magnetic resonance imaging, optokinetic responses and ganglion cell counts. Cell therapies for LHON therefore represent a promising therapeutic approach, and may be of particular utility in treating more advanced disease. PMID:24569607

SYNOPSIS Charcot Marie Tooth disease (CMT) is a heterogeneous group of inherited peripheral neuropathies in which the neuropathy is the sole or primary component of the disorder, as opposed to diseases in which the neuropathy is part of a more generalized neurological or multisystem syndrome. Due to the great genetic heterogeneity of this condition, it can be challenging for the general neurologist to diagnose patients with specific types of CMT. Here, we review the biology of the inherited peripheral neuropathies, delineate major phenotypic features of the CMT subtypes and suggest strategies for focusing genetic testing. PMID:23642725

Aim To determine the risk of non?arteritic anterior ischaemic opticneuropathy (NAION) after cataract extraction (CE) in the fellow eye of patients with prior unilateral NAION. Design Retrospective, cohort study. Methods Medical records of patients with NAION evaluated in our institution between 1 January 1986 and 31 December 2001 were reviewed to determine the onset of NAION and the time of CE. Patients were excluded if the date of NAION and CE was unreliable, or if CE in the fellow eye was performed before the unilateral NAION. Statistical analysis was performed by including fellow eye CE as a time?dependent covariate in a Cox proportional hazards regression model of NAION incidence in the fellow eye. Results Of the 325 eligible patients, 9 (53%) of 17 patients with NAION who underwent CE in the fellow eye developed fellow eye NAION, and 59 (19%) of 308 patients with NAION who did not undergo CE in the fellow eye developed fellow eye NAION. Cataract extraction in the fellow eye increased the risk of NAION occurrence in the fellow eye by 3.6?fold (Cox regression, p?=?0.001). Conclusions Patients with unilateral NAION are at a significantly higher risk of developing NAION in the fellow eye after CE. PMID:17446504

Leber hereditary opticneuropathy (LHON) has been shown to involve mutation(s) of mitochondrial DNA, yet there remain several confusing aspects of its inheritance not explained by mitochondrial inheritance alone, including male predominance, reduced penetrance, and a later age of onset in females. By extending segregation analysis methods to disorders that involve both a mitochondrial and a nuclear gene locus, the authors show that the available pedigree data for LHON are most consistent with a two-locus disorder, with one responsible gene being mitochondrial and the other nuclear and X chromosome-linked. Furthermore, they have been able to extend the two-locus analytic method and demonstrate that a proportion of affected females are likely heterozygous at the X chromosome-linked locus and are affected due to unfortunate X chromosome inactivation, thus providing an explanation for the later age of onset in females. The estimated penetrance for a heterozygous female is 0.11{plus minus}0.02. The calculated frequency of the X chromosome-linked gene for LHON is 0.l08. Among affected females, 60% are expected to be heterozygous, and the remainder are expected to be homozygous at the responsible X chromosome-linked locus.

The article concentrates on an issue of a diabetic autonomous neuropathy (DAN) in the gastrointestinal tract (GIT). It points out etiopathogenesis of diabetic polyneuropathy. It presents autonomous neuropathy in an overview where it also in more detail discusses this issue in the GIT. It highlights clinical picture and possible diagnostic and therapeutic ways of affecting individual parts of the gastrointestinal tract. PMID:15305631

Leber's hereditary opticneuropathy (LHON) is an optic nerve dysfunction resulting from mutations in mitochondrial DNA (mtDNA), which is transmitted in a maternal pattern of inheritance. It is caused by three primary point mutations: G11778A, G3460A and T14484C; in the mitochondrial genome. These mutations are sufficient to induce the disease, accounting for the majority of LHON cases, and affect genes that encode for the different subunits of mitochondrial complexes I and III of the mitochondrial respiratory chain. Other mutations are secondary mutations associated with the primary mutations. The purpose of this study was to determine MT-ND variations in Iranian patients with LHON. In order to determine the prevalence and distribution of mitochondrial mutations in the LHON patients, their DNA was studied using PCR and DNA sequencing analysis. Sequencing of MT-ND genes from 35 LHON patients revealed a total of 44 nucleotide variations, in which fifteen novel variations-A14020G, A13663G, C10399T, C4932A, C3893G, C10557A, C12012A, C13934T, G4596A, T12851A, T4539A, T4941A, T13255A, T14353C and del A 4513-were observed in 27 LHON patients. However, eight patients showed no variation in the ND genes. These mutations contribute to the current database of mtDNA polymorphisms in LHON patients and may facilitate the definition of disease-related mutations in human mtDNA. This research may help to understand the disease mechanism and open up new diagnostic opportunities for LHON. PMID:24158608

Hereditary neuropathies are classified into Charcot-Marie-Tooth disease (CMT), familial amyloid polyneuropathy (FAP), hereditary motor neuropathies (HMN) and hereditary sensory (and autonomic) neuropathies (HSAN). CMTs are furthermore classified into demyelinating neuropathies (CMT1), axonal neuropathies (CMT2) and intermediate form. Duplication of PMP22 (CMT1A) accounts for about 70% of CMT1 and MFN2 mutations account for 25% of CMT2. Genes involved in phosphoinositide regulation cause CMT4; MTMR2 mutation in CMT 4B1 and MTMR13/SBF2 mutation in CMT4B2. In addition to these genes, FIG4, which is a causative gene of pale tremor mouse, is newly identified as a gene for CMT4J. MFN2 and GDAP1 cause CMT2 or CMT4. These genes regulate mitochondrial fusion and fission. Altered axonal mitochondrial transport is suggested as the pathogenesis of the CMT. In animal model with pmp22 duplication, ascorbic acid seems to be effective to prevent disease progression. Nationwide trial of ascorbic acid therapy for CMT1A is now ongoing by the intractable neuropathy study group. Curcumin treatment educes apoptosis of cells that express PMP22 point mutation and partially mitigates the severe neuropathy phenotype of Trembler-J mouse model in a dose-dependent manner. Curcumin treatment may have a potential therapeutic role in CMT with PMP22 point mutation in humans. The high throughput system of diagnosis for CMT has been developed by employing a resequencing array system. PMID:19198150

Background: In the era of highly active antiretroviral therapy, sensory neuropathies have increased in prevalence. We have documented the frequency and profile of the two most common forms of sensory neuropathies associated with Human Immunodeficiency Virus (HIV) infection and looked into clinicoelectrophysiological correlates to differentiate the two entities. Methods: The study population comprised of all consecutive patients detected to be HIV positive and attending the Neurology outpatient department (from March 2011 to March 2012) who were aged ? 18 years and were able to give informed consent. The data were collected from the patient records (including CD4 counts and treatment details) and questionnaire based interview with each patient. All patients underwent detailed clinical examination and nerve conduction studies (NCSs). Results: Among the total study population of 50 patients, there were 31 men and 19 women. Thirty two patients were in age range of 21 - 40 years and rest were above 40 years. 25 were on antiretroviral therapy (18 on regimen containing zidovudine; seven on regimen containing stavudine). The mean duration of antiretroviral therapy was 16.6±8.4 months. Low CD4 counts (<200) were noted in 24 patients (13 of these were on antiretroviral therapy). Clinically, the patients were classified as asymptomatic (n=34) and symptomatic (n=16). Among the symptomatic patients, nine were on antiretroviral therapy since less than one year (seven of these were on regimen containing stavudine). Ten patients aged more than 40-years had symptomatic neuropathy. No significant correlation was found between low CD4 counts and symptomatic neuropathy (p=0.21). Impaired vibration (100%) and absent ankle jerks (75%) were commoner than reduced pin sensitivity (46.6%). Twenty two patients had abnormal NCS results (18 of these were on antiretroviral therapy). Axonal distal symmetrical sensory neuropathy was the commonest pattern noted in 14 patients who were receiving antiretroviral therapy. Subclinical involvement as evidenced by abnormal NCSs was noted in 5 asymptomatic patients who were all on antiretroviral therapy. Conclusion: Symptomatic neuropathy was seen predominantly in HIV patients who were on antiretroviral therapy. All patients receiving stavudine containing regimen had severe symptomatic neuropathy within 1 year. There was an increase in the likelihood of symptomatic neuropathy among patients aged > 40 years. Subclinical neuropathy was common in those on antiretroviral therapy. Axonal neuropathy was the commonest pattern noted in patients who were receiving antiretroviral therapy and demyelinating neuropathy in patients not on antiretroviral therapy. Surprisingly no significant correlation was found between low CD4 counts and symptomatic neuropathy. PMID:25177587

Background An increasing number of mitochondrial DNA (mtDNA) mutations, mainly in complex I genes, have been associated with variably overlapping phenotypes of Leber’s hereditary opticneuropathy (LHON), mitochondrial encephalomyopathy with stroke-like episodes (MELAS) and Leigh syndrome (LS). We here describe the first case in which the m.4171C>A/MT-ND1 mutation, previously reported only in association with LHON, leads also to a Leigh-like phenotype. Case presentation A 16-year-old male suffered subacute visual loss and recurrent vomiting and vertigo associated with bilateral brainstem lesions affecting the vestibular nuclei. His mother and one sister also presented subacute visual loss compatible with LHON. Sequencing of the entire mtDNA revealed the homoplasmic m.4171C>A/MT-ND1 mutation, previously associated with pure LHON, on a haplogroup H background. Three additional non-synonymous homoplasmic transitions affecting ND2 (m.4705T>C/MT-ND2 and m.5263C>T/MT-ND2) and ND6 (m.14180T>C/MT-ND6) subunits, well recognized as polymorphisms in other mtDNA haplogroups but never found on the haplogroup H background, were also present. Conclusion This case widens the phenotypic expression of the rare m.4171C>A/MT-ND1 LHON mutation, which may also lead to Leigh-like brainstem lesions, and indicates that the co-occurrence of other ND non-synonymous variants, found outside of their usual mtDNA backgrounds, may have increased the pathogenic potential of the primary LHON mutation. PMID:24884847

We reported here the clinical, genetic, and molecular characterization of Leber's hereditary opticneuropathy (LHON) with C5601T mutation in seven Chinese families. The ophthalmologic examinations of seven Chinese families who were clinically diagnosed LHON were conducted. Strikingly, these families exhibited very low penetrance of visual impairment, and the penetrance was 9.5%, 14.3%, 4.5%, 8.3%, 10.0%, 22.2% and 25.0%. Meanwhile, entire mitochondrial genome of seven probands was amplified by PCR using 24 pairs of oligonucleotide primers with overlapping fragments. Molecular analysis of mitochondrial DNA (mtDNA) in these pedigrees revealed the absence of three common LHON associated G11778A, G3460A and T14484C mutations but the presence of homoplastic LHON associated tRNAAla C5601T mutation in probands and other matrilineal relatives. These mtDNA polymorphism sites belongs to the Asian haplogroups G2, G2a1, G2a1, G2, G2b, G2a1 and G2. By analyzing mitochondrial genome, seven LHON families all carry the C5601T mutation. The C5601T mutation occurs at the highly conserved nucleotide (conventional position 59) of tRNAAla, thereby contributing to the structural formation and stabilization of functional tRNAs and leading to mitochondrial dysfunction involved in visual impairment. The incomplete penetrance of visual loss in these seven Chinese pedigrees strongly indicates that the tRNAAla C5601T mutation was itself insufficient to produce a clinical phenotype. The lack of functional mtDNA variants in these pedigrees ruled out the role of mitochondrial background in the phenotypic expression of visual loss. Therefore, nuclear backgrounds and environmental factors seem to be modifying factors for the phenotypic manifestation of the tRNAAla C5601T mutation in the seven Chinese families. PMID:22917908

To clarify the bioenergetic relevance of mtDNA mutations in Leber's hereditary opticneuropathy (LHON), we investigated affected individuals and healthy carriers from six Italian LHON families harboring the 11778/ND4 and the 3460/ND1 mtDNA mutations. The enzymatic activities of mitochondrial complex I and its sensitivity to the potent inhibitors rotenone and rolliniastatin-2 were studied in mitochondrial particles from platelets, in correlation with mtDNA analysis of platelets and leukocytes. In platelets homoplasmic for mutant mtDNA, both 11778/ND4 and 3460/ND1 mutations induced resistance to rotenone and the 3460/ND1 mutation also provoked a marked decrease in the specific activity of complex I. Individuals heteroplasmic in platelets for either mutation showed normal biochemical features, indicating functional complementation of wild-type mtDNA. There was no correlation between the clinical status and mtDNA homo/heteroplasmy in platelets, but the biochemical features correlated with the mitochondrial genotype of platelets. In some cases, the degree of mtDNA heteroplasmy differed in platelets and leukocytes from the same individual with a prevalence of wild-type mtDNA in the platelets. These results imply that biochemical studies on mitochondrial diseases should always be integrated with mtDNA analysis of the same tissue investigated and also suggest that the mtDNA analysis on the leukocyte fraction, as usually performed in LHON, does not necessarily reflect the mutant genotype level of other tissues. The differential tissue heteroplasmy may be more relevant than previously thought in determining disease penetrance. PMID:9191778

The term "diabetic neuropathy" refers to many varieties of neuropathies, including diabetic peripheral neuropathies (DPNs). DPNs are categorized into generalized and focal/multifocal varieties. Diabetic sensorimotor polyneuropathy (DSPN) and diabetic autonomic neuropathy (DAN) are typical DPNs, and their development is clearly linked to hyperglycemia and subsequent metabolic and ischemic change. On the other hand, other forms of neuropathy, including multifocal diabetic neuropathies (e.g., lumbosacral, thoracic, and cervical radiculoplexus neuropathies) are thought to be associated with inflammatory or immune processes. Diabetic patients can also develop chronic inflammatory demyelinating polyneuropathy (CIDP). CIDP in diabetic patients (DM-CIDP) should be ruled out, especially in patients with advanced DSPN. Recently, it was reported that diabetic radiculoplexus neuropathies as well as CIDP respond favorably to immunotherapy. Thus, these immune-mediated diabetic neuropathies are treatable, and should be differentiated from advanced DSPN. PMID:24523312

Ultrasonographic nerve enlargement has primarily been reported in patients with inflammatory neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy, Guillain-Barre syndrome, vasculitic neuropathy and leprosy. Nerve ultrasonography is a promising diagnostic supportive tool for inflammatory neuropathies. The ultrasonographic findings that are currently useful are 1) nerve enlargement primarily suggests the existence of inflammatory or demyelinating neuropathies and 2) for patients with CIDP or demyelinating Charcot-Marie-Tooth disease, the pattern of nerve enlargement is noted, and this pattern is useful for discriminating between these diseases. More precise evidence of ultrasonographic findings for inflammatory neuropathies should be established in the future. PMID:24607946

IMPORTANCE Establishing the natural history of G11778A Leber hereditary opticneuropathy (LHON) is important to determine the optimal end points to assess the safety and efficacy of a planned gene therapy trial. OBJECTIVE To use the results of the present natural history study of patients with G11778A LHON to plan a gene therapy clinical trial that will use allotopic expression by delivering a normal nuclear-encoded ND4 gene into the nuclei of retinal ganglion cells via an adeno-associated virus vector injected into the vitreous. DESIGN, SETTING, AND PARTICIPANTS A prospective observational study initiated in 2008 was conducted in primary and referral institutional practice settings. Participants included 44 individuals with G11778A LHON, recruited between September 2008 and March 2012, who were evaluated every 6 months and returned for 1 or more follow-up visits (6-36 months) as of August 2012. EXPOSURES Complete neuro-ophthalmic examination and main measures. MAIN OUTCOMES AND MEASURES Visual acuity, automated visual field testing, pattern electroretinogram, and spectral-domain optical coherence tomography. RESULTS Clinical measures were stable during the follow-up period, and visual acuity was as good as or better than the other visual factors used for monitoring patients. Based on a criterion of 15 or more letters from the Early Treatment Diabetic Retinopathy Study chart, 13 eyes of 8 patients (18%) improved, but 24 months after the onset of symptoms, any further improvements were to no better than 20/100. Acuity recovery occurred in some patients despite continued marked retinal nerve fiber layer thinning indistinguishable from that in patients who did not recover visual acuity. CONCLUSIONS AND RELEVANCE Spontaneous improvement of visual acuity in patients with G11778A LHON is not common and is partial and limited when it occurs, so improvements in vision with adeno-associated virus-mediated gene therapy of a synthetic wild-type ND4 subunit gene should be possible to detect with a reasonable sample size. Visual acuity appears to be the most suitable primary end point for the planned clinical trial. PMID:24525545

We report the discovery of an anomalous flare in a bright blazar, namely, PKS 0208-512, one of the targets of the Yale/SMARTS optical-near-IR (OIR) monitoring program of Fermi blazars. We identify three intervals during which PKS 0208-512 undergoes outbursts at OIR wavelengths lasting for {approx}>3 months. Its brightness increases and then decreases again by at least 1 mag in these intervals. In contrast, the source undergoes bright phases in GeV energies lasting {approx}>1 month during intervals 1 and 3 only. The OIR outburst during interval 2 is comparable in brightness and temporal extent to the OIR flares during intervals 1 and 3, which do have {gamma}-ray counterparts. By analyzing the {gamma}-ray, OIR, and supporting multi-wavelength variability data in details, we speculate that the OIR outburst during interval 2 was caused by a change in the magnetic field without any change in the total number of emitting electrons or Doppler factor of the emitting region. Alternatively, it is possible that the location of the outburst in the jet during interval 2 was closer to the black hole where the jet is more compact and the bulk Lorentz factor of the material in the jet is smaller. We also discuss the complex OIR spectral behavior during these three intervals.

Hereditary neuropathies are classified into several subtypes according to clinical, electrophysiologic and pathologic findings. Recent genetic studies have revealed their phenotypic and genetic diversities. In the primary peripheral demyelinating neuropathies (CMT1), at least 15 genes have been associated with the disorders; altered dosage or point mutation of PMP22, GJB1, MPZ, EGR2, MTMR2, NDRG1, PRX, SOX10, GDAP1 and MTMR13/SBF2. In the primary peripheral axonal neuropathies (CMT2), at least 10 genes have been associated with these disorders; NEFL, KIF1B, MFN2, GAN1, LMNA, RAB7, GARS, TDP1, APTX, and SETX. In addition, some mutations in GJB1, MPZ, GDAP1 and NEFL also present with clinical and electrophysiologic findings of CMT2. Patients with TDP1, APTX or SETX mutations share common clinical findings; autosomal recessive inheritance, cerebellar ataxia, and axonal neuropathy. These genes are suspected to be related to DNA/RNA repair and induce cell death especially in neuronal cells. In addition to the above diseases, we have reported a new type of NMSNP (MIM# * 604484) characterized by proximal dominant neurogenic atrophy, obvious sensory nerve involvement and the gene locus on 3q12.3. Here, we summarize the genetic bases of hereditary neuropathies and attempt to highlight significant genotype-phenotype correlations with a special interest in nonsense-mediated mRNA decay pathway. PMID:15651351

The induction of peripheral neuropathy is a common factor in limiting therapy with chemotherapeutic drugs. Little is known\\u000a about the mechanisms responsible for the development of neuropathy. Depending on the substance used, a pure sensory and painful\\u000a neuropathy (with cisplatin, oxaliplatin, carboplatin) or a mixed sensorimotor neuropathy with or without involvement of the\\u000a autonomic nervous system (with vincristine, taxol, suramin)

Summary This review attempts to outline the present understanding of diabetic autonomic neuropathy. The clinical features have been increasingly recognised but knowledge of the localization and morphology of the lesions and their pathogenesis remains fragmentary. A metabolic causation as postulated in somatic nerves accords best with clinical observations. Most bodily systems, particularly the cardiovascular, gastrointestinal and urogenital, are involved with added

Neuropathy is the most common and debilitating complication of diabetes and results in pain, decreased motility, and amputation. Diabetic neuropathy encompasses a variety of forms whose impact ranges from discomfort to death. Hyperglycemia induces oxidative stress in diabetic neurons and results in activation of multiple biochemical pathways. These activated pathways are a major source of damage and are potential therapeutic targets in diabetic neuropathy. Though therapies are available to alleviate the symptoms of diabetic neuropathy, few options are available to eliminate the root causes. The immense physical, psychological, and economic cost of diabetic neuropathy underscores the need for causally targeted therapies. This review covers the pathology, epidemiology, biochemical pathways, and prevention of diabetic neuropathy, as well as discusses current symptomatic and causal therapies and novel approaches to identify therapeutic targets. PMID:18616962

Inherited autonomic neuropathies are a rare group of disorders associated with sensory dysfunction. As a group they are termed the "hereditary sensory and autonomic neuropathies" (HSAN). Classification of the various autonomic and sensory disorders is ongoing. In addition to the numerical classification of four distinct forms proposed by Dyck and Ohta (1975), additional entities have been described. The best known and most intensively studied of the HSANs are familial dysautonomia (Riley-Day syndrome or HSAN type III) and congenital insensitivity to pain with anhidrosis (HSAN type IV). Diagnosis of the HSANs depends primarily on clinical examinations and specific sensory and autonomic assessments. Pathologic examinations are helpful in confirming the diagnosis and in differentiating between the different disorders. In recent years identification of specific genetic mutations for some disorders has aided diagnosis. Replacement or definitive therapies are not available for any of the disorders so that treatment remains supportive and directed toward specific symptoms. PMID:15088259

Giant axonal neuropathy (GAN) is a distal sensorimotor neuropathy, characterized by neurofilamentous axonal swellings, with usual onset at 2 to 3 years of age. We report a case of congenital GAN with hypotonia at birth. At 7 months of age, nerve conduction studies showed almost complete lack of sensory and motor responses in the lower extremities. A sural nerve biopsy specimen disclosed absence of myelinated axons. Autopsy, following death at 15 months of age, revealed axonal swellings in peripheral nerves and distal degeneration of long spinal cord tracts. The neurofilamentous content of the axonal swellings was confirmed by Glees-Marsland staining and immunoperoxidase reaction with antibodies to neurofilaments. Axonal swellings did not stain with periodic acid-Schiff and were not seen in the cerebral cortex or brain stem, distinguishing this process from infantile neuroaxonal dystrophy. This patient illustrates congenital GAN with subsequent rapid progression. PMID:2990373

Greyhound dogs exposed to oral acrylamide for a period of eight weeks developed a sensorimotor peripheral neuropathy that had many features in common with acrylamide neuropathy seen in other species. Most of the animals also developed the clinical and radiological features of megaoesophagus. The association of neuropathy and megaoesophagus suggests that an axonopathy of the vagus may be an aetiological factor in this disorder. Images PMID:6273507

The typical clinical manifestation of vasculitic peripheral neuropathy is sensory-dominant multiple mononeuropathy, although it can progress to distal-dominant sensorimotor polyneuropathy. It is painful in most cases. Peripheral nerves may be the most prone to produce symptoms of the vasculitis. Nerve conduction studies show reduced amplitude of M wave or sensory nerve action potential, which depends on the degree of injury of a nerve examined. Wallerian degeneration can cause pseudo-conduction block in the acute stage and temporal dispersion in the chronic stage. However, a definite diagnosis requires histological confirmation. Combined biopsy of the sural nerve and the peroneus brevis muscle can be performed by a single incision. Skin biopsy can also be performed. To increase the diagnostic yield, biopsy specimens are prepared in different manners to observe as many cross sections as possible: frozen unfixed, formalin-fixed paraffin-embedded, and glutaraldehyde-fixed epon embedded specimens, as well as teased fiber preparation of a nerve. Vasculitic peripheral neuropathy usually results from small-vessel vasculitis. There are still controversies regarding the classification of vasculitides. Differential diagnosis of vasculitis includes infection and lymphoma. Delayed diagnosis and treatment of neuropathy result in the impairment of ADL and QOL. Recovery from axonal degeneration usually takes time and is not always possible. Treatment includes corticosteroid, cyclophosphamide, and intravenous immunoglobulin administration; however, the intensity of treatment depends on the disease activity of vasculitis. PMID:24200608

This work was undertaken to study the prevalence of auditory neuropathy among deaf subjects “as diagnosed by objective tests for peripheral neuropathy” together with their performance using the cochlear implant (CI) device. Thirty-five adult CI subjects versus twenty subjects with sensorineural hearing loss of both genders and of variable etiology of hearing loss were included. Electrophysiological testing of peripheral nerves

Peripheral neuropathies are a heterogeneous group of diseases affecting peripheral nerves. The causes are multiple: hereditary, metabolic, infectious, inflammatory, toxic, traumatic. The temporal profile includes acute, subacute and chronic conditions. The majority of peripheral neuropathies cause mainly muscle weakness and sensory loss, positive sensory symptoms and sometimes pain. When pain is present, however, it is usually extremely intense and among the most disabling symptoms for the patients. In addition, the neurological origin of the pain is often missed and patients receive inadequate or delayed specific treatment. Independently of the disease causing the peripheral nerve injury, pain originating from axonal pathology or ganglionopathy privileges neuropathies affecting smaller fibres, a clinical observation that points towards abnormal activity within nociceptive afferents as a main generator of pain. Natural activation of blood vessels or perineurial nociceptive network by pathology also causes intense pain. Pain of this kind, i.e. nerve trunk pain, is among the heralding symptoms of inflammatory or ischemic mononeuropathy and for its intensity represents itself a medical emergency. Neuropathic pain quality rekindles the psychophysical experience of peripheral nerves intraneural microstimulation i.e. a combination of large and small fibres sensation temporally distorted compared to physiological perception evoked by natural stimuli. Pins and needles, burning, cramping mixed with numbness, and tingling are the wording most used by patients. Nociceptive pain instead is most often described as aching, deep and dull. Good command of peripheral nerve anatomy and pathophysiology allows timely recognition of the different pain components and targeted treatment, selected according to intensity, type and temporal profile of the pain. PMID:18615140

Streptosotocin-induced diabetes in rats is accompanied by the development of diabetic complications such as neuropathies. [2-14C]serotonin and [U-14C]GABA release from the neurotransmitter pre-loaded synaptosomes showed significant elevation. Aldose reductase inhibitors (AL-1576, sorbinil) administration leads to partial restoration of serotonin and GABA release, while picamilon restored only GABA release. It was shown that Na+,K(+)-ATPase activities decreased in synaptosomes, synaptic membranes and sciatic nerve of diabetic rats compared to control. Administration of AL-1576 normalized Na+, K(+)-ATPase activity, while sorbinil and picamilon less effectively. Sorbitol level are increased in streptozotocin-diabetic rats as compared to control. The picamilon and aldose reductase inhibitors administration to diabetic rats is accompanied by the partial reduction of brain sorbitol level. The findings confirm the important role of picamilon and aldose reductase inhibitors in the prevention and treatment of diabetic neuropathy. PMID:10599142

background Other than glycemic control, there are no treatments for diabetic neuropathy. Thus, identifying potentially modifiable risk factors for neuropathy is crucial. We studied risk factors for the development of distal symmetric neuropathy in 1172 patients with type 1 diabetes mellitus from 31 centers participating in the European Diabetes (EURODIAB) Prospective Complications Study. methods Neuropathy was assessed at baseline (1989

Autonomic neuropathy, once considered to be the Cinderella of diabetes complications, has come of age. The autonomic nervous system innervates the entire human body, and is involved in the regulation of every single organ in the body. Thus, perturbations in autonomic function account for everything from abnormalities in pupillary function to gastroparesis, intestinal dysmotility, diabetic diarrhea, genitourinary dysfunction, amongst others. "Know autonomic function and one knows the whole of medicine!" It is now becoming apparent that before the advent of severe pathological damage to the autonomic nervous system there may be an imbalance between the two major arms, namely the sympathetic and parasympathetic nerve fibers that innervate the heart and blood vessels, resulting in abnormalities in heart rate control and vascular dynamics. Cardiac autonomic neuropathy (CAN) has been linked to resting tachycardia, postural hypotension, orthostatic bradycardia and orthostatic tachycardia (POTTS), exercise intolerance, decreased hypoxia-induced respiratory drive, loss of baroreceptor sensitivity, enhanced intraoperative or perioperative cardiovascular lability, increased incidence of asymptomatic ischemia, myocardial infarction, and decreased rate of survival after myocardial infarction and congestive heart failure. Autonomic dysfunction can affect daily activities of individuals with diabetes and may invoke potentially life-threatening outcomes. Intensification of glycemic control in the presence of autonomic dysfunction (more so if combined with peripheral neuropathy) increases the likelihood of sudden death and is a caveat for aggressive glycemic control. Advances in technology, built on decades of research and clinical testing, now make it possible to objectively identify early stages of CAN with the use of careful measurement of time and frequency domain analyses of autonomic function. Fifteen studies using different end points report prevalence rates of 1% to 90%. CAN may be present at diagnosis, and prevalence increases with age, duration of diabetes, obesity, smoking, and poor glycemic control. CAN also cosegregates with distal symmetric polyneuropathy, microangiopathy, and macroangiopathy. It now appears that autonomic imbalance may precede the development of the inflammatory cascade in type 2 diabetes and there is a role for central loss of dopaminergic restraint on sympathetic overactivity. Restoration of dopaminergic tone suppresses the sympathetic dominance and reduces cardiovascular events and mortality by close to 50%. Cinderella's slipper can now be worn! PMID:24095132

The pain and discomfort caused by peripheral neuropathy is one of the most common reasons that cancer patients stop their treatment early. Researchers are working to improve new screening, treatment, and prevention options for patients.

In this trial, researchers are testing the ability of an antioxidant supplement called alpha-lipoic acid to prevent peripheral neuropathy caused by the platinum-containing drugs cisplatin and oxaliplatin.

Three patients with peripheral neuropathy and mixed or immune complex cryoglobulinaemia are reported. The significance of mixed cryoglobulinaemia and the pathogenesis of the peripheral neuropathy are discussed. Images PMID:4360402

Despite improvements in the identification of causes of peripheral neuropathy, idiopathic polyneuropathy remains common. Medication\\u000a and toxic neuropathy account for a small but important percentage of potentially preventable or reversible causes of neuropathy.\\u000a New drugs that can induce neuropathy have been approved over the past several years, including the anticancer agents bortezomib,\\u000a ixabepilone, and oxaliplatin. We review the neurotoxic effects

The genetic neuropathies are a clinically and genetically heterogeneous group of diseases of which the most common types are Charcot–Marie–Tooth disease (CMT), the hereditary sensory and autonomic neuropathies and the distal hereditary motor neuropathies. More than 30 causative genes have been described, making an accurate genetic diagnosis increasingly possible. Although no specific therapies are yet available, research into their pathogenesis

Why is peripheral neuropathy common but mild in many mitochondrial disorders, and why is it, in some cases, the predominant or only manifestation? Although this question remains largely unanswered, recent advances in cellular and molecular biology have begun to clarify the importance of mitochondrial functioning and distribution in the peripheral nerve. Mutations in proteins involved in mitochondrial dynamics (ie, fusion and fission) frequently result in a Charcot-Marie-Tooth phenotype. Peripheral neuropathies with different phenotypic presentations occur in mitochondrial diseases associated with abnormalities in mitochondrial DNA replication and maintenance, or associated with defects in mitochondrial respiratory chain complex V. Our knowledge of mitochondrial disorders is rapidly growing as new nuclear genes are identified and new phenotypes described. Early diagnosis of mitochondrial disorders, essential to provide appropriate genetic counselling, has become crucial in a few treatable conditions. Recognising and diagnosing an underlying mitochondrial defect in patients presenting with peripheral neuropathy is therefore of paramount importance. PMID:24050734

Previously reported cases of peripheral neuropathies occurring during almitrine therapy had only a few weeks follow-up after having stopped the drug. We have studied clinical and electrophysiological data 6 to 12 months after almitrine had been given up in 9 patients from a group of 14 whose epidemiologic, clinical, electrophysiological and pathological data had been registered. In 7 of them, without any chronic respiratory deficiency, almitrine was administered as almitrine bismésilate and raubasine, and in 7 others (6 with chronic respiratory deficiency) as almitrine bismesilate alone. In patients who had another possible cause of neuropathy, clinical disorders appeared after a lesser total quantity of almitrine (p less than 0.05). Clinical data were suggestive of sensory peripheral neuropathies of feet and lower third of legs. Electrophysiological data suggested distal axonopathy in spite of the absence of denervation: amplitudes of sensory potentials were reduced and nerve conduction velocities were moderately decreased. Biopsies revealed mild neurogenic atrophy of muscles and distal axonopathy. Clinical improvement was very slow and 6 to 12 months later, most of the patients still presented decreased vibration sense and ankle reflexes loss, but all of them were still improving. Amplitudes of sensory potentials and sensory nerve conduction velocities were significantly improved (p less than 0.05) but motor nerve conduction velocities were not (p greater than 0.05). Our study shows: 1) clinical, electrophysiological and pathological data similar to those previously reported; 2) subclinical disturbances of motor functions in lower limbs and sensory functions in upper limbs; 3) some patients presented with unusual signs: posture tremor (3 cases), painful legs and moving toes (1 case); 4) peripheral neuropathies may occur during almitrine therapy even in patients without any chronic respiratory insufficiency; 5) peripheral neuropathies occurred with lower doses in patients with other factors predisposing to neuropathies; 6) patients' improvement was very slow; 7) in 9 cases the imputability of these peripheral neuropathies to almitrine is plausible. We suggest not to prescribe almitrine without caution, especially in patients with other factors of neuropathy. Treatment should be regularly interrupted. PMID:2889253

Bortezomib is a proteasome inhibitor demonstrating substantial activity in multiple myeloma. One of its key toxicities is peripheral neuropathy, which is reversible in most patients. The possibility that bortezomib might in rare cases induce severe neuropathies by auto-inflammatory mechanisms remains controversial. We report here the case of a 65-year-old female myeloma patient who was initially treated with bortezomib, doxorubicin, and dexamethasone (PAD). At the end of the second cycle of PAD, the patient presented with a rapid and severe onset of paresis of the left arm, accompanied by progressive sensory neuropathy and increasing neuropathic pain. After an extensive neurological work-up, including electrophysiological and laboratory evaluations as well as magnet resonance tomography imaging, we diagnosed an inflammatory autoimmune neuropathy, presumably induced by bortezomib, with accentuation of the left arm nerve plexus. We subsequently initiated regular treatment with polyvalent immunoglobulins, which gradually improved the neurological symptoms. In conclusion, the identification of an inflammatory autoimmune neuropathy, presumably associated with bortezomib, is a rare but important complication. An extensive neurological examination should be performed in patients who develop severe or unusual sensory or motor deficits under therapy with bortezomib, so as to differentiate autoimmune from toxic neuropathies, as therapeutic strategies differ for each. PMID:21553020

Leber’s Hereditary OpticNeuropathy (LHON) is one of the commonest mitochondrial diseases. It causes total blindness, and predominantly affects young males. For the disease to develop, it is necessary for an individual to carry one of the primary mtDNA mutations 11778G>A, 14484T>C or 3460G>A. However these mutations are not sufficient to cause disease, and they do not explain the characteristic features of LHON such as the higher prevalence in males, incomplete penetrance, and relatively later age of onset. In order to explore the roles of nuclear encoded mitochondrial proteins in development of LHON, we applied a proteomic approach to samples from affected and unaffected individuals from 3 pedigrees and from 5 unrelated controls. Two-dimensional electrophoresis followed by MS/MS analysis in the mitochondrial lysate identified 17 proteins which were differentially expressed between LHON cases and unrelated controls, and 24 proteins which were differentially expressed between unaffected relatives and unrelated controls. The proteomic data were successfully validated by western blot analysis of 3 selected proteins. All of the proteins identified in the study were mitochondrial proteins and most of them were down regulated in 11778G>A mutant fibroblasts. These proteins included: subunits of OXPHOS enzyme complexes, proteins involved in intermediary metabolic processes, nucleoid related proteins, chaperones, cristae remodelling proteins and an anti-oxidant enzyme. The protein profiles of both the affected and unaffected 11778G>A carriers shared many features which differed from those of unrelated control group, revealing similar proteomic responses to 11778G>A mutation in both affected and unaffected individuals. Differentially expressed proteins revealed two broad groups: a cluster of bioenergetic pathway proteins and a cluster involved in protein quality control system. Defects in these systems are likely to impede the function of retinal ganglion cells, and may lead to the development of LHON in synergy with the primary mtDNA mutation. PMID:25215595

Leber's Hereditary OpticNeuropathy (LHON) is one of the commonest mitochondrial diseases. It causes total blindness, and predominantly affects young males. For the disease to develop, it is necessary for an individual to carry one of the primary mtDNA mutations 11778G>A, 14484T>C or 3460G>A. However these mutations are not sufficient to cause disease, and they do not explain the characteristic features of LHON such as the higher prevalence in males, incomplete penetrance, and relatively later age of onset. In order to explore the roles of nuclear encoded mitochondrial proteins in development of LHON, we applied a proteomic approach to samples from affected and unaffected individuals from 3 pedigrees and from 5 unrelated controls. Two-dimensional electrophoresis followed by MS/MS analysis in the mitochondrial lysate identified 17 proteins which were differentially expressed between LHON cases and unrelated controls, and 24 proteins which were differentially expressed between unaffected relatives and unrelated controls. The proteomic data were successfully validated by western blot analysis of 3 selected proteins. All of the proteins identified in the study were mitochondrial proteins and most of them were down regulated in 11778G>A mutant fibroblasts. These proteins included: subunits of OXPHOS enzyme complexes, proteins involved in intermediary metabolic processes, nucleoid related proteins, chaperones, cristae remodelling proteins and an anti-oxidant enzyme. The protein profiles of both the affected and unaffected 11778G>A carriers shared many features which differed from those of unrelated control group, revealing similar proteomic responses to 11778G>A mutation in both affected and unaffected individuals. Differentially expressed proteins revealed two broad groups: a cluster of bioenergetic pathway proteins and a cluster involved in protein quality control system. Defects in these systems are likely to impede the function of retinal ganglion cells, and may lead to the development of LHON in synergy with the primary mtDNA mutation. PMID:25215595

Subdural hemorrhage (SDH) can manifest various neurologic symptoms. However, SDH presenting with only hand weakness has rarely been reported. We report two SDH cases with only hand weakness mimicking peripheral neuropathy. Since SDH can present with hand weakness only, we suggest the clinicians to do a careful history taking and recommend a CT scan in the elderly patients.

In 30 patients with diabetic neuropathy sensory potentials in the median nerve, motor conduction in the lateral popliteal and median nerves, and electromyographic findings in distal and proximal muscles were compared with the severity of symptoms and signs. All patients had abnormalities in at least one of the electrophysiological parameters. The sensory potentials were the most sensitive indicator of subclinical

Four patients were observed who developed similar episodes of peripheral neuropathy following prolonged treatment with chloroquine phosphate. This previously unreported toxic reaction consisted of bilateral loss of knee and ankle reflexes and weakness of the quadriceps muscles. Gradual return to normal followed withdrawal of the chloroquine. Other toxic reactions to the drug are reviewed. PMID:14052974

Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I

A new peripheral neuropathy activities measure, the Overall Neuropathy Limitations Scale (ONLS), was derived by modifying the Overall Disability Sum Score (ODSS) slightly. Its inter?rater reliability was found to be high and its correlation with the ODSS (r?=?0.97), 36?item Short Form Questionnaire Physical Component Summary Score, and participation and impairment measures was significant. Acceptable responsiveness (standardised response mean 0.76) was shown by the ONLS. The results obtained from the questionnaire agreed closely with those obtained from observation of the tasks on the ONLS, but were not equivalent. The simplicity of the ODSS is shared by the ONLS, but the ONLS has better content validity and less ceiling effect, which may make it more useful for clinical practice and research. PMID:16574730

The peripheral nervous system (PNS) comprises the cranial nerves, the spinal nerves with their roots and rami, dorsal root ganglia neurons, the peripheral nerves, and peripheral components of the autonomic nervous system. Cell-mediated or antibody-mediated immune attack on the PNS results in distinct clinical syndromes, which are classified based on the tempo of illness, PNS component(s) involved, and the culprit antigen(s) identified. Insights into the pathogenesis of autoimmune neuropathy have been provided by ex vivo immunologic studies, biopsy materials, electrophysiologic studies, and experimental models. This review article summarizes earlier seminal observations and highlights the recent progress in our understanding of immunopathogenesis of autoimmune neuropathies based on data from animal models. PMID:24615441

Inherited neuropathies are clinically and genetically heterogeneous. At least 28 genes and 12 loci have been associated with Charcot-Marie-Tooth disease (CMT) and related inherited neuropathies. Most causes of inherited neuropathy have been discovered by positional cloning technique and in the past two years, the pace of CMT gene discovery has accelerated. Genetic studies have revealed the following gene mutations as the causes of inherited neuropathies; PMP22, MPZ, EGR2, SOX10, SIMPLE/LITAF, ARHGEF10 for CMT1 (autosomal dominant demyelinating form); GDAP1, MTMR2, SBF2/MTMR13, KIAA1985, NDRG1 PRX for CMT4 (autosomal recessive demyelinating form), MFN2, KIF1B, RAB7, GARS, NEFL, HSPB1, HSPB8 for CMT2 (autosomal dominant axonal form); LMNA, GAN1, KCC3, TDP1, APTX, SETX for AR-CMT2 (autosomal recessive axonal form); GIB1 for CMTX (X-linked CMT); DNM2 for CMT-DI (autosomal dominant CMT with intermediate nerve conduction velocities); and DHH for minifascicular neuropathy. These discovered CMT causing genes/proteins include those which show unpredictable correlations with the peripheral nervous system. However, these genes/proteins are definitely important for the peripheral nerve, and their discovery should pave the way for dramatic progress in the understanding of peripheral nerve biology. On the other hand, genotype-phenotype correlations of these genes are also important in order to understand the pathomechanisms of inherited neuropathy. Because, based on mutation studies, a large number of genes associated with both the CMT1/4 and CMT2 forms have been identified, it is usually difficult to predict the causative gene based on clinical information from patients without specific complications. To clarify the specific features and molecular mechanisms of five diseases that we previously reported, we reviewed recent progress in HMSN-P linked to chromosome 3, CMT4F caused by PRX, CMT4A caused by GDAP1, CMT4B2 caused by SBF2/MTMR13, and SCAN1 caused by TDP1. HMSN-P is characterized by late onset, proximal dominant severe muscle weakness, fasciculations, muscle cramp and sensory involvement. HMSN-P is a primary neuronopathy. Mutations in periaxin are associated with a broad spectrum of demyelinating neuropathies including DSS, a sensory dominant form and early onset slowly progressive CMT. Pathologically, loss of myelinated fibers, demyelination, small onion bulb formations, tomacula formation and myelin foldings were seen in sural nerves. Absence of septate like junction in the paranodal loop suggests that periaxin could be required for the adhesion complex. GDAP1 is a relatively common cause of CMT4. Half of reported patients showed the demyelinating form, while the rest showed the axonal form. The typical feature of CMT4A is paresis of the vocal cords and diaphragm. CMT4B2 is characterized by autosomal recessive, juvenile onset glaucoma and focally folded myelin in sural nerves. SBF2/MTMR13 mutations cause CMT4B2. Early onset glaucoma was seen in patients with nonsense mutations. SBF2/MTMR13 and MTMR2, which is the cause of CMT4B1, could be acting on the same 3-phosphoinositide signaling pathway. Clinical phenotypes of patients with TDP1, APTX, or SETX mutations share common clinical findings, namely cerebellar ataxia and axonal neuropathy. TDP1 and aprataxin both act on the single strand break repair pathway, with TDP1 working specifically on topoisomerase I related SSBR. Senataxin is a RNA helicase acting on RNA maturation and termination in yeast. Since these three proteins share a common pathway, disruption in any of them could induce a delay in the transcription process. The low rate of protein supply could lead to deaths of large neuronal cells. PMID:16541790

Amyloid neuropathies occur in a context of hereditary (FAP) or acquired amyloidosis. They present usually as severe and progressive\\u000a polyneuropathy and carry a poor prognosis. Most FAP are associated with endoneurial deposits of variant transthyretin (TTR)\\u000a with substitution of one aminoacid and are secondary to a point mutation of the TTR gene. Portugal is the main endemic area\\u000a of TTR-FAP,

Type II mixed cryoglobulinemia is sustained by an oligoclonal production of IgM sharing rheumatoid activity and can be associated\\u000a with renal, cutaneous, rheumatologic or neurological manifestations. Peripheral neuropathy is a major cause of morbidity in\\u000a hepatitis C virus-associated mixed cryoglobulinemia and is often refractory to any treatment. Rituximab induces a selective\\u000a depletion of IgM-producing B cells, and both case reports

The patient was a 48-year-old alcoholic man with no contributory family history. At age 36 he had developed sensory dominant polyneuropathy with highly impaired temperature sensation and deep sensation in the lower extremities, recurrent ulcers of the toes, and sexual impotence. A sural nerve biopsy at this time revealed marked loss of myelinated fibers with relative preservation of the population of unmyelinated fibers. Subsequently, he developed muscle atrophy of the lower thighs, urinary incontinence, and Wernicke's encephalopathy, and became non-ambulatory at age 44. The peripheral nerve conduction findings suggested predominantly axonal degeneration. The entire course was characterized by alternative progression and partial recovery influenced by his alcohol intake and nutritional state. Alcoholic neuropathy is a major cause of solitary acrodystrophic neuropathy (ADN). Manifestations of autonomic and motor neuropathy are more marked in alcoholic ADN than in HSAN-I, and central nervous system involvement is the hallmark of alcoholic ADN. In the treatment of patients with alcoholic ADN, attention should be paid to diabetes mellitus, malnutritional state, and vitamin deficiency, which frequently complicate alcoholism. PMID:8386536

Inflammatory neuropathies represent disabling human autoimmune disorders with considerable disease variability. Animal models provide insights into defined aspects of their disease pathogenesis. Forkhead box P3 (FoxP3)+ regulatory T lymphocytes (Treg) are anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. Dysfunction or a reduced frequency of Tregs have been associated with different human autoimmune disorders. We here analyzed the functional relevance of Tregs in determining disease manifestation and severity in murine models of autoimmune neuropathies. We took advantage of the DEREG mouse system allowing depletion of Treg with high specificity as well as anti-CD25 directed antibodies to deplete Tregs in mice in actively induced experimental autoimmune neuritis (EAN). Furthermore antibody-depletion was performed in an adoptive transfer model of chronic neuritis. Early Treg depletion increased clinical EAN severity both in active and adoptive transfer chronic neuritis. This was accompanied by increased proliferation of myelin specific T cells and histological signs of peripheral nerve inflammation. Late stage Treg depletion after initial disease manifestation however did not exacerbate inflammatory neuropathy symptoms further. We conclude that Tregs determine disease severity in experimental autoimmune neuropathies during the initial priming phase, but have no major disease modifying function after disease manifestation. Potential future therapeutic approaches targeting Tregs should thus be performed early in inflammatory neuropathies. PMID:25286182

Inflammatory neuropathies represent disabling human autoimmune disorders with considerable disease variability. Animal models provide insights into defined aspects of their disease pathogenesis. Forkhead box P3 (FoxP3)+ regulatory T lymphocytes (Treg) are anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. Dysfunction or a reduced frequency of Tregs have been associated with different human autoimmune disorders. We here analyzed the functional relevance of Tregs in determining disease manifestation and severity in murine models of autoimmune neuropathies. We took advantage of the DEREG mouse system allowing depletion of Treg with high specificity as well as anti-CD25 directed antibodies to deplete Tregs in mice in actively induced experimental autoimmune neuritis (EAN). Furthermore antibody-depletion was performed in an adoptive transfer model of chronic neuritis. Early Treg depletion increased clinical EAN severity both in active and adoptive transfer chronic neuritis. This was accompanied by increased proliferation of myelin specific T cells and histological signs of peripheral nerve inflammation. Late stage Treg depletion after initial disease manifestation however did not exacerbate inflammatory neuropathy symptoms further. We conclude that Tregs determine disease severity in experimental autoimmune neuropathies during the initial priming phase, but have no major disease modifying function after disease manifestation. Potential future therapeutic approaches targeting Tregs should thus be performed early in inflammatory neuropathies. PMID:25286182

Three patients with the sicca syndrome and chronic sensory neuropathy are described; in two of them neuropathy was the presenting feature of the disease. The sicca syndrome can give rise to a characteristic neurological syndrome comprising areflexia and asymmetrical sensory loss, particularly of proprioception, in the limbs. This is often associated with tonic pupils and trigeminal anaesthesia. PMID:3007674

X-ray examinations of the feet, knees, and hands were performed on 20 diabetics with severe neuropathy and 20 diabetics with no evidence of neuropathy but with a similar mean age and duration of diabetes. All were under 53 years old with no clinical evidence of peripheral vascular disease. Medial arterial calcification was much more common and extensive in the patients

Gastric emptying was studied in 12 diabetic patients, six with and six without objective evidence of autonomic neuropathy and in 20 non-diabetic controls, using a double isotope scinti-scanning technique which differentiated between solid and liquid emptying. Three patients with autonomic neuropathy exhibited gastric stasis, although this was detected by conventional radiology in only one. Neither the patients with stasis nor

Summary Peripheral blood flow is known to be qualitatively increased in diabetic patients with neuropathy. We have measured the actual blood flow in the feet of diabetic patients with neuropathy using non-invasive mercury strain gauge plethysmography and Doppler sonogram techniques and shown that it is increased on average five times above normal at an ambient temperature of 20 °–22 °C. Moreover,

Stroke is the third most common cause of mortality and is one of the most common causes of morbidity in the world. Entrapment neuropathies may cause morbidity after stroke. In this study, we aimed to evaluate the development of entrapment neuropathies in severe stroke patients within the chronic stages of the event. Thirty-two patients with first ever ischemic or hemorrhagic stroke were included in the study. The nerve conduction studies were performed at least 6 months after the event. Ten age- and sex-matched healthy subjects were evaluated as control subjects. Twelve patients (37.5%) had median nerve neuropathy at the wrist, and 12 patients (37.5%) had ulnar nerve neuropathy at the elbow in the symptomatic extremities. Eight patients (25%) had median nerve neuropathy at the wrist, and 6 patients (18.7%) had ulnar nerve neuropathy at the elbow in the asymptomatic extremities. Our results confirm that in chronic stroke patients, the entrapment neuropathies may be an important cause for morbidity, and these entrapment neuropathies could be seen bilaterally but more prominent in the paretic sides. PMID:22353993

The inflammatory neuropathies are a large diverse group of immune-mediated neuropathies that are amenable to treatment and may be reversible. Their accurate diagnosis is essential for informing the patient of the likely course and prognosis of the disease, informing the treating physician of the appropriate therapy and informing the scientific community of the results of well-targeted, designed and performed clinical

\\u000a \\u000a Spinocerebellar ataxia with axonal neuropathy (SCAN1) is an autosomal recessive disorder caused by a specific point mutation\\u000a (c.1478A>G, p.H493R) in the tyrosyl-DNA phosphodiesterase (TDP1) gene. Functional and genetic studies suggest that this mutation, which disrupts the active site of the Tdp1 enzyme, causes\\u000a disease by a combination of decreased catalytic activity and stabilization of the normally transient covalent Tdp1-DNA intermediate.

Giant axonal neuropathy (GAN) is a rare genetic disease of childhood involving the central and peripheral nervous systems. Axonal loss with several giant axons filled with neurofilaments is the main histopathological feature of peripheral nerve biopsies in this disease. Routine neuroimaging studies reveal diffuse hyperintensities in cerebral and cerebellar white matter. In this case report, the authors present the brain magnetic resonance spectroscopic features (normal N-acetylaspartate/creatine and increased choline/creatine and myoinositol/creatine ratios), which might indicate the absence of neuroaxonal loss and the presence of significant demyelination and glial proliferation in white matter, of an 11-year-old boy diagnosed with GAN. PMID:14569833

The spectrum of chronic dysimmune neuropathies has widened well beyond chronic demyelinating polyradiculoneuropathy (CIDP). Pure motor (multifocal motor neuropathy), sensorimotor with asymmetrical involvement (multifocal acquired demylinating sensory and motor neuropathy), exclusively distal sensory (distal acquired demyelinating sensory neuropathy) and very proximal sensory (chronic immune sensory polyradiculopathy) constitute the variants of CIDP. Correct diagnosis of these entities is of importance in terms of initiation of appropriate therapy as well as prognostication of these patients. The rates of detection of immune-mediated neuropathies with monoclonal cell proliferation (monoclonal gammopathy of unknown significance, multiple myeloma, etc.) have been facilitated as better diagnostic tools such as serum immunofixation electrophoresis are being used more often. Immune neuropathies associated with malignancies and systemic vasculitic disorders are being defined further and treated early with better understanding of the disease processes. As this field of dysimmune neuropathies will evolve in the future, some of the curious aspects of the clinical presentations and response patterns to different immunosuppressants or immunomodulators will be further elucidated. This review also discusses representative case studies. PMID:21808468

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are the main enzymes that produce oxidative stress, which plays an important role in painful diabetic neuropathy. Curcumin has been reported to exert an antinociceptive effect in a rat model of diabetic neuropathy by suppressing oxidative stress in the spinal cord. However, it remains unknown whether the mechanism by which curcumin ameliorates diabetic neuropathy can be attributed to spinal NADPH oxidases. This study was designed to determine the effect of curcumin on diabetic neuropathy and to investigate its precise mechanism in relation to NADPH oxidase-mediating oxidative stress in the spinal cord. Diabetic neuropathy was induced in Sprague-Dawley rats by intraperitoneal injection with 1% streptozotocin (STZ; 60 mg/kg). After the onset of diabetic neuropathy, a subset of the diabetic rats received daily intragastric administrations of curcumin (200mg/kg) or intraperitoneal injections of apocynin (2.5mg/kg) for 14 consecutive days, whereas other diabetic rats received equivalent volumes of normal saline (NS). STZ resulted in diabetic neuropathy with hyperglycemia and a lower paw withdrawal threshold (PWT), accompanied by elevations in the expression of the NADPH oxidase subunits p47(phox) and gp91(phox) and in the levels of hydrogen peroxide (H2O2) and malondialdehyde (MDA) and a reduction in superoxide dismutase (SOD) activity (P<0.05) in the spinal cord. Both curcumin and apocynin ameliorated diabetic neuropathy. In conclusion, curcumin attenuated neuropathic pain in diabetic rats, at least partly by inhibiting NADPH oxidase-mediating oxidative stress in the spinal cord. PMID:24370596

The genetic neuropathies are a clinically and genetically heterogeneous group of diseases of which the most common types are Charcot-Marie-Tooth disease (CMT), the hereditary sensory and autonomic neuropathies and the distal hereditary motor neuropathies. More than 30 causative genes have been described, making an accurate genetic diagnosis increasingly possible. Although no specific therapies are yet available, research into their pathogenesis has revolutionised our understanding of the peripheral nervous system and allowed the development of rational approaches to therapy. The first therapeutic trials in CMT are currently underway. This review will suggest an approach to the diagnosis of these disorders and provide an update on new therapies. PMID:19917815

To clarify the specific features and molecular mechanisms of five diseases that we previously reported, we reviewed recent progress in HMSN-P linked to chromosome 3, CMT4F caused by PRX, CMT4A caused by GDAP1, CMT4B2 caused by SBF2/MTMR13F, and SCAN1 caused by TDP1. HMSN-P is characterized by late onset, proximal dominant severe muscle weakness, fasciculations, muscle cramp and sensory involvement. HMSN-P is a primary neuronopathy. Mutations in periaxin are associated with a broad spectrum of demyelinating neuropathies including DSS, a sensory dominant form and early onset slowly progressive CMT. Pathologically, loss of myelinated fibers, demyelination, small onion bulb formations, tomacula formation and myelin foldings were seen in sural nerves. Absence of septate like junction in the paranodal loop suggests that periaxin could be required for the adhesion complex. GDAP1 is a relatively common cause of CMT4. Half of reported patients showed the demyelinating form, while the rest showed the axonal form. The typical feature of CMT4A is paresis of the vocal cords and diaphragm. CMT4B2 is characterized by autosomal recessive, juvenile onset glaucoma and focally folded myelin in sural nerves. SBF2/MTMR13 mutations cause CMT4B2. Early onset glaucoma was seen in patients with nonsense mutations. SBF2/MTMR13 and MTMR2, which is the cause of CMT4B1, could be acting on the same 3-phosphoinositide signaling pathway. Clinical phenotypes of patients with SCAN1 showed cerebellar ataxia and axonal neuropathy. TDP1 acts on the single strand break repair pathway, and works specifically on topoisomerase I related SSBR. Disruption of TDP1 could induce a delay in the transcription process. The low rate of protein supply could lead to deaths of large neuronal cell. PMID:17432174

Inherited neuropathy is a group of common neurologic disorders with heterogeneous clinical presentations and genetic causes. Detailed neuromuscular evaluations, including nerve conduction studies, laboratory testing, and histopathologic examination, can assist in identification of the inherited component beyond family history. Genetic testing increasingly enables definitive diagnosis of specific inherited neuropathies. Diagnosis, however, is often complex, and neurologic disability may have both genetic and acquired components in individual patients. The decision of which genetic test to order or whether to order genetic tests is often complicated, and the strategies to maximize the value of testing are evolving. Apart from rare inherited metabolic neuropathies, treatment approaches remain largely supportive. We provide a clinical update of the various types of inherited neuropathies, their differential diagnoses, and distinguishing clinical features (where available). A framework is provided for clinical evaluations, including the inheritance assessment, electrophysiologic examinations, and specific genetic tests. PMID:23801417

Amyloid neuropathies of acquired or genetic origin are disabling and life-threatening, until recently there were few treatment options available. Poor prognosis is related to progressive neuropathy and associated, although often underdiagnosed, cardiac involvement in specific transthyretin (TTR) gene mutations. Recent progress has modified prognosis and management of amyloid neuropathies. In TTR-familial amyloidosis with polyneuropathy, major changes have occurred over the last 30 years: better knowledge concerning genetics, phenotypes and epidemiology, and the advent of possible treatments. Liver transplantation, first performed in 1990, stopped disease progression, thus doubling survival in early onset V30M patients. More recently tetramer stabilizers (Tafamidis and Diflunisal) showed a significant reduction of progression of neuropathic scores; Tafamidis is now recommended in Stage I patients. Two multicentric clinical trials are now ongoing to evaluate TTR gene silencing by antisense Oligonucleotides (ASO) or siRNA. In the near future we should have new therapeutical options for patients with amyloid neuropathy. PMID:25416603

This article is a primer on the pathophysiology and clinical evaluation of peripheral neuropathy for the radiologist. Magnetic resonance neurography has utility in the diagnosis of many focal peripheral nerve lesions. When combined with history, examination, electrophysiology, and laboratory data, future advancements in high-field magnetic resonance neurography may play an increasingly important role in the evaluation of patients with peripheral neuropathy. PMID:24210312

The article deals with issues of diabetic autonomous neuropathy (DAN) in the urogenital tract (UGT), and brings attention to the ethiopathogenesis of diabetic polyneuropathy. It provides a synopsis of autonomous neuropathy and deals, in more detail, with its manifestations in the UGT. The different symptoms of the disorder are addressed, the need for timely diagnosis is pointed out as the prerequisite for a successful therapy, and the necessity for interdisciplinary cooperation in dealing with this health issue is exposed. PMID:18630632

Purpose Patients with ulnar neuropathy of unclear etiology occasionally present with lesion extension from elbow to upper arm level on MRI. This study investigated whether MRI thereby distinguishes multifocal neuropathy from focal-compressive neuropathy at the elbow. Methods This prospective study was approved by the institutional ethics committee and written informed consent was obtained from all participants. 122 patients with ulnar mononeuropathy of undetermined localization and etiology by clinical and electrophysiological examination were assessed by MRI at upper arm and elbow level using T2-weighted fat-saturated sequences at 3T. Twenty-one patients were identified with proximal ulnar nerve lesions and evaluated for findings suggestive of disseminated neuropathy (i) subclinical lesions in other nerves, (ii) unfavorable outcome after previous decompressive elbow surgery, and (iii) subsequent diagnosis of inflammatory or other disseminated neuropathy. Two groups served as controls for quantitative analysis of nerve-to-muscle signal intensity ratios: 20 subjects with typical focal ulnar neuropathy at the elbow and 20 healthy subjects. Results In the group of 21 patients with proximal ulnar nerve lesion extension, T2-w ulnar nerve signal was significantly (p<0.001) higher at upper arm level than in both control groups. A cut-off value of 1.92 for maximum nerve-to-muscle signal intensity ratio was found to be sensitive (86%) and specific (100%) to discriminate this group. Ten patients (48%) exhibited additional T2-w lesions in the median and/or radial nerve. Another ten (48%) had previously undergone elbow surgery without satisfying outcome. Clinical follow-up was available in 15 (71%) and revealed definitive diagnoses of multifocal neuropathy of various etiologies in four patients. In another eight, diagnoses could not yet be considered definitive but were consistent with multifocal neuropathy. Conclusion Proximal ulnar nerve T2 lesions at upper arm level are detected by MRI and indicate the presence of a non-focal disseminated neuropathy instead of a focal compressive neuropathy. PMID:23166762

Initiation of organophosphorus-induced delayed neuropathy (OPIDN) is thought to consist of two molecular events involving the phosphorylation of the target enzyme, neurotoxic esterase or neuropathy target enzyme (NTE), and a subsequent 'aging' reaction which transforms the inhibi...

Abnormal neuronal calcium (Ca2+) homeostasis has been implicated in numerous diseases of the nervous system. The pathogenesis of two increasingly common disorders of the peripheral nervous system, namely neuropathic pain and diabetic polyneuropathy, has been associated with aberrant Ca2+ channel expression and function. Here we review the current state of knowledge regarding the role of Ca2+ dyshomeostasis and associated mitochondrial dysfunction in painful and diabetic neuropathies. The central impact of both alterations of Ca2+ signalling at the plasma membrane and also intracellular Ca2+ handling on sensory neuron function is discussed and related to abnormal endoplasmic reticulum performance. We also present new data highlighting sub-optimal axonal Ca 2+ signalling in diabetic neuropathy and discuss the putative role for this abnormality in the induction of axonal degeneration in peripheral neuropathies. The accumulating evidence implicating Ca2+ dysregulation with both painful and degenerative neuropathies, along with recent advances in understanding of regional variations in Ca2+ channel and pump structures, makes modulation of neuronal Ca2+ handling an increasingly viable approach for therapeutic interventions against the painful and degenerative aspects of many peripheral neuropathies. PMID:20034667

control. While certain conditions may contribute to the development of peripheral neuropathy--diabetes#12;The Center for Peripheral Neuropathy Department of Neurology The University of Chicago 5841 South Maryland Avenue, MC2030 Chicago, Illinois 60637 Director, Center for Peripheral Neuropathy Brian

Peripheral neuropathies are among the most common neurological diseases and have numerous causes, including diabetes, alcohol, hereditary, toxic, metabolic, infectious, inflammatory, ischaemic and paraneoplastic. Often, however, no definitive cause is identified and the condition is termed idiopathic neuropathy. Here we describe a patient who was initially diagnosed with idiopathic sciatic neuropathy but who was eventually diagnosed with prostate cancer. This

Summary To optimize care in the evaluation of peripheral neuropathy, we sought to define which tests drive expenditures and the role of the provider type. We investigated test utilization and expenditures by provider type in those with incident neuropathy in a nationally representative elderly, Medicare population. Multivariable logistic regression was used to determine predictors of MRI and electrodiagnostic utilization. MRIs of the neuroaxis and electrodiagnostic tests accounted for 88% of total expenditures. Mean and aggregate diagnostic expenditures were higher in those who saw a neurologist. Patients who saw a neurologist were more likely to receive an MRI and an electrodiagnostic test. MRIs and electrodiagnostic tests are the main contributors to expenditures in the evaluation of peripheral neuropathy, and should be the focus of future efficiency efforts. PMID:24175158

Pneumocephalus is a common occurrence after cranial surgery, with patients typically remaining asymptomatic from a moderate amount of intracranial air. Postsurgical pneumocephalus rarely causes focal neurological deficits; furthermore, cranial neuropathy from postsurgical pneumocephalus is exceedingly uncommon. Only 3 cases have been previously reported that describe direct cranial nerve compression from intracranial air resulting in an isolated single cranial nerve deficit. The authors present a patient who developed dysconjugate eye movements from bilateral oculomotor nerve palsy. Direct cranial nerve compression occurred as a result of postoperative pneumocephalus in the interpeduncular cistern. The isolated cranial neuropathy gradually recovered as the intracranial air was reabsorbed. PMID:24151506

Diabetic neuropathies consist of a variety of syndromes resulting from different types of damage to peripheral or cranial nerves. Although distal symmetric polyneuropathy is most common type of diabetic neuropathy, there are many other subtypes of diabetic neuropathies which have been defined since the 1800’s. Included in these descriptions are patients with proximal diabetic, truncal, cranial, median, and ulnar neuropathies. Various theories have been proposed for the pathogenesis of these neuropathies. The treatment of most of these requires tight and stable glycemic control. Spontaneous recovery is seen in most of these conditions with diabetic control Immunotherapies have been tried in some of these conditions but are quite controversial. PMID:23642718

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal-dominant disorder associated with recurrent mononeuropathies following compression or trivial trauma. Reports on sciatic neuropathy as the presenting manifestation of HNPP are very scarce. We report on a 21-year-old previously healthy man who was admitted with sensorimotor deficits in his left leg. He had no history of preceding transient episodes of weakness or sensory loss. Clinical and electrophysiological examinations were consistent with sciatic neuropathy. Cerebrospinal fluid investigation and MRI of the nerve roots, plexus, and sciatic nerve did not indicate the underlying aetiology. When extended electrophysiological tests revealed multiple subclinical compression neuropathies in the upper limbs, HNPP was contemplated and eventually confirmed by genetic testing. PMID:25326571

Purpose: Speech perception in participants with auditory neuropathy (AN) was systematically studied to answer the following 2 questions: Does noise present a particular problem for people with AN: Can clear speech and cochlear implants alleviate this problem? Method: The researchers evaluated the advantage in intelligibility of clear speech over…

Pupillary function was investigated in 36 insulin-dependent diabetics and 36 controls matched for age and sex. About half of the diabetics had evidence of peripheral somatic or autonomic neuropathy, or both. The diabetic patients had abnormally small pupil diameters in the dark and less fluctuation in pupil size (hippus) during continuous illumination than the controls. They also had reduced reflex

Purpose: Auditory neuropathy spectrum disorder, or ANSD, can be a confusing diagnosis to physicians, clinicians, those diagnosed, and parents of children diagnosed with the condition. The purpose of this review is to provide the reader with an understanding of the disorder, the limitations in current tools to determine site(s) of lesion, and…

Diabetic peripheral neuropathy (DPN) is one of the most commonly occurring major complications of diabetes. The disease may manifest in several clinical patterns: most frequently as distal symmetrical sensory polyneuropathy. Guidelines are available for the diagnosis of DPN by the primary care physician. These recommend that a review of diabetic patients, including a questionnaire and inspection and neurological examination of

Long lists of causes of peripheral neuropathy make peripheral nerve disease a dry and uninspiring subject. A simple scheme based on the answers to just six questions should enable the clinician to recognise characteristic patterns, investigate relevant subgroups appropriately, and identify treatable disorders quickly: which systems are involved? What is the distribution of weakness? What is the nature of the

The paper focuses on the issues of diabetic autonomic neuropathy in the gastrointestinal tract. It describes the aethiopathogenesis of diabetic polyneuropathy. More detailed discussion is then provided with respect to gastrointestinal tract. The clinical picture and options available for the diagnosis and treatment when various parts of the gastrointestinal tract are involvement are examined. PMID:21612065

Charcot-Marie-Tooth disease (CMT) 2A with optic atrophy is referred to as hereditary motor and sensory neuropathy type VI (HMSN VI) and is caused by mitofusin 2 gene (MFN2) mutation. In patients with MFN2 related CMT, central nervous system is known to be also involved and cerebral white matter is mostly involved. We report a patient confirmed as HMSN VI who had isolated bilateral middle cerebellar peduncular lesions in brain MRI. PMID:25258575

Charcot-Marie-Tooth disease (CMT) 2A with optic atrophy is referred to as hereditary motor and sensory neuropathy type VI (HMSN VI) and is caused by mitofusin 2 gene (MFN2) mutation. In patients with MFN2 related CMT, central nervous system is known to be also involved and cerebral white matter is mostly involved. We report a patient confirmed as HMSN VI who had isolated bilateral middle cerebellar peduncular lesions in brain MRI.

Gall bladder motor function is impaired in some patients with diabetes. It has been suggested that the abnormalities of gall bladder motility are confined to those patients with autonomic neuropathy. Erythromycin, a motilin receptor agonist, causes gall bladder contraction in both normal subjects and patients with gall stones with impaired gall bladder emptying. The effect of erythromycin on gall bladder motility in seven patients with diabetes with an autonomic neuropathy, six patients with diabetes without autonomic neuropathy, and 17 normal subjects was studied using ultrasound. There was no significant difference in gall bladder fasting volume between the three groups, but the patients with diabetes with autonomic neuropathy had impaired postprandial gall bladder emptying compared with normal subjects (percentage emptied (SEM) 40 (10.3)% v 64 (2.8)%, p < 0.01) and those with autonomic neuropathy (48 (7.7)%, NS). Erythromycin produced a dramatic reduction in gall bladder fasting volume in patients with diabetes with an autonomic neuropathy, compared with either normal subjects or patients with diabetes without autonomic neuropathy (percentage reduction 62 (4.6)% in patients with autonomic neuropathy, v 37 (17.6)% in those without autonomic neuropathy, and 26 (7.3)% in the normal subjects, (p < 0.02) and returned gall bladder emptying to normal in all patients with impaired emptying. The pronounced effect of erythromycin in diabetic autonomic neuropathy suggests denervation supersensitivity and that the action of erythromycin on the gall bladder is neurally modulated. PMID:8174966

IMPORTANCE Patients with rare diseases and complex clinical presentations represent a challenge for clinical diagnostics. Genomic approaches are allowing the identification of novel variants in genes for very rare disorders, enabling a molecular diagnosis. Genomics is also revealing a phenotypic expansion whereby the full spectrum of clinical expression conveyed by mutant alleles at a locus can be better appreciated. OBJECTIVE To elucidate the molecular cause of a complex neuropathy phenotype in 3 patients by applying genomic sequencing strategies. DESIGN, SETTING, AND PARTICIPANTS Three affected individuals from 2 unrelated families presented with a complex neuropathy phenotype characterized by axonal sensorimotor neuropathy and microcephaly. They were recruited into the Centers for Mendelian Genomics research program to identify the molecular cause of their phenotype. Whole-genome, targeted whole-exome sequencing, and high-resolution single-nucleotide polymorphism arrays were performed in genetics clinics of tertiary care pediatric hospitals and biomedical research institutions. MAIN OUTCOMES AND MEASURES Whole-genome and whole-exome sequencing identified the variants responsible for the patients’ clinical phenotype. RESULTS We identified compound heterozygous alleles in 2 affected siblings from 1 family and a homozygous nonsense variant in the third unrelated patient in the vaccinia-related kinase 1 gene (VRK1). In the latter subject, we found a common haplotype on which the nonsense mutation occurred and that segregates in the Ashkenazi Jewish population. CONCLUSIONS AND RELEVANCE We report the identification of disease-causing alleles in 3 children from 2 unrelated families with a previously uncharacterized complex axonal motor and sensory neuropathyaccompanied by severe nonprogressive microcephaly and cerebral dysgenesis. Our data raise the question of whether VRK1 mutations disturb cell cycle progression and may result in apoptosis of cells in the nervous system. The application of unbiased genomic approaches allows the identification of potentially pathogenic mutations in unsuspected genes in highly genetically heterogeneous and uncharacterized neurological diseases. PMID:24126608

EMG, which consists of nerve conduction studies and needle electromyography, is an essential diagnostic tool in the evaluation of patients with suspected peripheral neuropathy. Many neurologists order an EMG for all patients with suspected peripheral neuropathy. Not surprisingly, evidence now exists that shows EMG is a major driver of health care costs associated with neuropathy diagnoses. As neurologic practice evolves from fee for service to value-based compensation, neurologists will need to justify the diagnostic utility of EMG (outcome) relative to its cost. While carefully performed studies of diagnostic utility in many patient populations are lacking, a robust literature provides guidance regarding the potential role and limitations of EMG in neuropathy diagnosis as well as the pitfalls referring providers and electrodiagnostic consultants must consider. Do all neuropathy patients need an EMG at least once? This article attempts to answer this question using an illustrative case to highlight critical factors every neurologist must consider before ordering an EMG for neuropathy diagnosis. PMID:25299292

Charcot-Marie-Tooth (CMT) disease is the most common inherited motor and sensory neuropathy. Previous studies have shown that neuropathic pain is an occasional symptom of CMT referred by CMT patients. However, neuropathic pain is not considered a significant symptom in CMT patient and no researchers have studied profoundly the pathophysiology of neuropathic pain in CMT. Here, we highlight the relationship between CMT disease and neuropathic pain via previous several studies. PMID:24278891

Recent progress in human genetics and neurobiology has led to the identification of various mutations in particular myelin genes as the cause for many of the known inherited demyelinating peripheral neuropathies. Mutations in 3 distinct myelin genes, PMP22, P0, and connexin 32 cause the 3 major demyelinating subtypes of Charcot-Marie-Tooth (CMT) disease, CMT1A, CMT1B and CMTX, respectively. In addition, a reduction in the gene dosage of PMP22 causes hereditary neuropathy with liability to pressure palsies (HNPP), while particular point mutations in PMP22 and P0 cause the severe Dejerine-Sottas (DS) neuropathy. A series of spontaneous and genetically engineered rodent mutants for genes for the above-mentioned myelin constituents are now available and their suitability to serve as models for these still untreatable diseases is an issue of particular interest. The spontaneous mutants Trembler-J and Trembler, with point mutations in PMP22, reflect some of the pathological alterations seen in CMT1A and DS patients, respectively. Furthermore, engineered mutants that either over or underexpress particular myelin genes are suitable models for patients who are similarly compromised in the gene dosage of the corresponding genes. In addition, engineered mutants heterozygously or homozygously deficient in the myelin component P0 show the pathology of distinct CMT1B and DS patients, respectively, while Cx32 deficient mice develop pathological abnormalities similar to those of CMTX patients. Mutants that mimic human peripheral neuropathies might allow the development of strategies to alleviate the symptoms of the diseases, and help to define environmental risk factors for aggravation of the disease. In addition, such mutants might be instrumental in the development of strategies to cure the diseases by gene therapy. PMID:9418989

Between 25% and 62% of patients with idiopathic peripheral neuropathy are reported to have prediabetes, and among individuals with prediabetes 11–25% are thought to have peripheral neuropathy, and 13–21% have neuropathic pain. Population-based studies suggest a gradient for the prevalence of neuropathy, being highest in patients with manifest diabetes mellitus, followed by individuals with impaired glucose tolerance then impaired fasting

Small-fiber neuropathy manifests in a variety of different diseases and often results in symptoms of burning pain, shooting\\u000a pain, allodynia, and hyperesthesia. Diagnosis of small-fiber neuropathy is determined primarily by the history and physical\\u000a exam, but functional neurophysiologic testing and skin biopsy evaluation of intraepidermal nerve-fiber density can provide\\u000a diagnostic confirmation. Management of small-fiber neuropathy depends on the underlying etiology

The present epidemic of diabetes is resulting in a worldwide increase in cardiovascular and microvascular complications including retinopathy. Current thinking has focused on local influences in the retina as being responsible for development of this diabetic complication. However, the contribution of circulating cells in maintenance, repair, and dysfunction of the vasculature is now becoming appreciated. Diabetic individuals have fewer endothelial progenitor cells (EPCs) in their circulation and these cells have diminished migratory potential, which contributes to their decreased reparative capacity. Using a rat model of type 2 diabetes, we show that the decrease in EPC release from diabetic bone marrow is caused by bone marrow neuropathy and that these changes precede the development of diabetic retinopathy. In rats that had diabetes for 4 mo, we observed a dramatic reduction in the number of nerve terminal endings in the bone marrow. Denervation was accompanied by increased numbers of EPCs within the bone marrow but decreased numbers in circulation. Furthermore, denervation was accompanied by a loss of circadian release of EPCs and a marked reduction in clock gene expression in the retina and in EPCs themselves. This reduction in the circadian peak of EPC release led to diminished reparative capacity, resulting in the development of the hallmark feature of diabetic retinopathy, acellular retinal capillaries. Thus, for the first time, diabetic retinopathy is related to neuropathy of the bone marrow. This novel finding shows that bone marrow denervation represents a new therapeutic target for treatment of diabetic vascular complications. PMID:19934019

??Neuropathy associated with Diabetes is increasing at epidemic rates throughout the world. Traditionally, this neuropathy causes loss of protective sensation leading to ulceration, infection ,… (more)

Retinal nerve fiber layer (RNFL) thinning and optic nerve head cupping are key diagnostic features of glaucomatous opticneuropathy. The higher resolution of the recently introduced SD-OCT offers enhanced visualization and improved segmentation of the retinal layers, providing a higher accuracy in identification of subtle changes of the optic disc and RNFL thinning associated with glaucoma.

Intravenous immunoglobulin (IVIg) infusions may provide clinical benefits in multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP). The short delay in the clinical response to IVIg therapy is not consistent with a process of remyelination or axonal regeneration. We assessed whether or not the efficacy of IVIg infusions in MMN and CIDP could reflect changes in axonal membrane

ORIGINAL ARTICLE Peripheral Neuropathy in Military Aircraft Maintenance Workers in Australia Maya/4 the magnitude of diabetes. Age, height, and diabetes were all significant and strong predictors in most models. Conclusion: This study highlights chronic persisting peripheral neuropathy in a population of aircraft

An investigation of the mechanism of damage to the peripheral nervous system and central nervous system in diabetes mellitus (DM) is highly important in current neurological research. Auditory neuropathy is a hearing disorder in which the auditory brainstem evoked potential is absent or severely abnormal. This study investigated auditory neuropathy caused by streptozotocin in mouse model. In order to assess

Peripheral neuropathies are common and frequently debilitating disorders linked to degeneration of peripheral nerves that supply mainly the distal muscles of the extremities. Due to the diverse origin of the pathology (genetic, systemic or environmental), peripheral neuropathies exhibit different clinical forms: acute or chronic, symmetrical or asymmetrical, demyelinating or axonal. In the last 30 years, to gain insight into cellular

The study of diabetic neuropathy has been primarily in Europids, despite the high prevalence of diabetes in other populations. We set out to ascertain the prevalence of diabetic neuropathy and its risk factors in the island nation of Mauritius. Population surveys were carried out in 1987 and 1992 in Mauritius to establish the prevalence of Type 2 diabetes. In the

Approximately 1 in 2500 Americans suffer from Charcot-Marie-Tooth (CMT) disease. The underlying disease mechanisms are unique in most forms of CMT, with many point mutations on various genes causing a toxic accumulation of misfolded proteins. Symptoms of the disease often present within the first two decades of life, with CMT1A patients having reduced compound muscle and sensory action potentials, slow nerve conduction velocities, sensory loss, progressive distal weakness, foot and hand deformities, decreased reflexes, bilateral foot drop and about 5% become wheelchair bound. In contrast, the ultra-rare disease Giant Axonal Neuropathy (GAN) is frequently described as a recessively inherited condition that results in progressive nerve death. GAN usually appears in early childhood and progresses slowly as neuronal injury becomes more severe and leads to death in the second or third decade. There are currently no treatments for any of the forms of CMTs or GAN. We suggest that further clinical studies should analyse electrical impedance myography as an outcome measure for CMT. Further, additional quality of life (QoL) assessments for these CMTs are required, and we need to identify GAN biomarkers as well as develop new genetic testing panels for both diseases. We propose that using the Global Registry of Inherited Neuropathy (GRIN) could be useful for many of these studies. Patient advocacy groups and professional organizations (such as the Hereditary Neuropathy Foundation (HNF), Hannah's Hope Fund (HHF), The Neuropathy Association (TNA) and the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) can play a central role in educating clinicians and patients. Undertaking these studies will assist in the correct diagnosis of disease recruiting patients for clinical studies, and will ultimately improve the endpoints for clinical trials. By addressing obstacles that prevent industry investment in various forms of inherited neuropathies, we can envision treatment options for these rare diseases in the near future. PMID:24860645

Approximately 1 in 2500 Americans suffer from Charcot-Marie-Tooth (CMT) disease. The underlying disease mechanisms are unique in most forms of CMT, with many point mutations on various genes causing a toxic accumulation of misfolded proteins. Symptoms of the disease often present within the first two decades of life, with CMT1A patients having reduced compound muscle and sensory action potentials, slow nerve conduction velocities, sensory loss, progressive distal weakness, foot and hand deformities, decreased reflexes, bilateral foot drop and about 5% become wheelchair bound. In contrast, the ultra-rare disease Giant Axonal Neuropathy (GAN) is frequently described as a recessively inherited condition that results in progressive nerve death. GAN usually appears in early childhood and progresses slowly as neuronal injury becomes more severe and leads to death in the second or third decade. There are currently no treatments for any of the forms of CMTs or GAN. We suggest that further clinical studies should analyse electrical impedance myography as an outcome measure for CMT. Further, additional quality of life (QoL) assessments for these CMTs are required, and we need to identify GAN biomarkers as well as develop new genetic testing panels for both diseases. We propose that using the Global Registry of Inherited Neuropathy (GRIN) could be useful for many of these studies. Patient advocacy groups and professional organizations (such as the Hereditary Neuropathy Foundation (HNF), Hannah's Hope Fund (HHF), The Neuropathy Association (TNA) and the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) can play a central role in educating clinicians and patients. Undertaking these studies will assist in the correct diagnosis of disease recruiting patients for clinical studies, and will ultimately improve the endpoints for clinical trials. By addressing obstacles that prevent industry investment in various forms of inherited neuropathies, we can envision treatment options for these rare diseases in the near future. PMID:24860645

In this review, we delineate clinical, electrodiagnostic, and radiographic features of ulnar mononeuropathies. Ulnar neuropathy at the elbow (UNE) is most commonly due to lesions at the level of the retroepicondylar groove (RTC), with approximately 25% at the humeroulnar arcade (HUA). The term 'cubital tunnel syndrome' should be reserved for the latter. The diagnostic accuracy of nerve conduction studies is limited by biological (e.g. low elbow temperature) and technical factors. Across-elbow distance measurements greater than 10 cm improve diagnostic specificity at the expense of decreased sensitivity. Short-segment incremental studies can differentiate lesions at the HUA from those at the RTC. PMID:23177030

The past 15 years have witnessed the identification of more than 25 genes responsible for inherited neuropathies in humans, many associated with primary alterations of the myelin sheath. A remarkable body of work in patients, as well as animal and cellular models, has defined the clinical and molecular genetics of these illnesses and shed light on how mutations in associated genes produce the heterogeneity of dysmyelinating and demyelinating phenotypes. Here, we review selected recent developments from work on the molecular mechanisms of these disorders and their implications for treatment strategies. PMID:18803325

Peripheral diabetic neuropathy (PDN) is one of the most devastating complications of diabetes mellitus. The pathogenesis of\\u000a PDN involves hyperglycemia-initiated mechanisms as well as other factors, i.e., impaired insulin signaling, hypertension,\\u000a disturbances of fatty acid and lipid metabolism. This review describes new findings in animal and cell culture models:\\u000a \\u000a \\u000a \\u000a 1. \\u000a \\u000a Supporting the importance of previously established hyperglycemia-initiated mechanisms, such as

Demyelinating optic neuritis (ON) is the most common cause of opticneuropathy typically presenting with a subacute painful visual loss. In 20% of patients with multiple sclerosis (MS), ON is the presenting symptom and half of the patients with isolated ON develop MS within 15 years. The diagnosis of ON plays an important role in neurological practice. A correct and early diagnosis is necessary to ensure optimal further investigations and treatment. Other causes of opticneuropathies such as connective tissue disorders, infectious diseases, tumours or ischaemic neuropathies are less frequent but clinical and therapeutic management can differ dramatically. We present five patients admitted to our hospital with suspected demyelinating ON, but the clinical work up revealed different causes of opticneuropathy. We discuss the differential diagnosis of ON and clinical red flags that require careful diagnostic assessment of other diseases. A workflow for the diagnosis of opticneuropathies is presented. PMID:21694809

Twenty four men with insulin dependent diabetes and different degrees of autonomic neuropathy were studied to establish the response of the QT interval to various heart rates. Nine men with autonomic neuropathy had a longer QT interval than 13 healthy individuals and 15 patients who had diabetes without, or with only mild, autonomic neuropathy. Those with autonomic neuropathy also had

The presence of antiganglioside antibodies is associated with several neurologic disorders. These antibodies recognize several epitopes, generally saccharides present in these glucolipids. The presence of antiGM antibodies has been described in certain clinical syndromes, the main one being multifocal motor neuropathy with and without conduction blocks. The frequency of antiGM1 class IgM antibody falls between 20 and 80% in this disease. Axon predominant Guillain-Barré syndrome is also associated with high titers of antiGM1 antibodies, although in this case class IgG is implicated. The most important association to date has been established between Miller-Fisher syndrome and the presence of antiGQ1b antibodies. Several authors have reported molecular similarities among these gangliosides and bacterial lipopolysaccharides, mainly Campylobacter iejuni. The principal aims in the study of antiganglioside antibodies are to establish their pathogenic role as well as the clinical usefulness of analyzing for them, and to discover new specificities that aid in the diagnosis and classification of neuropathies, whether they are predominantly motor disorders or chronic sensory ones. PMID:9044577

Diabetic peripheral neuropathy (DPN) refers to the nerve damage that can occur in diabetes patients. It most often affects the extremities, such as the feet, and can lead to peripheral vascular disease, deformity, infection, ulceration, and even amputation. The key to managing diabetic foot is prevention and early detection. Unfortunately, current existing diagnostic techniques are mostly based on patient sensations and exhibit significant inter- and intra-observer differences. We have developed a computer aided diagnostic (CAD) system for diabetic peripheral neuropathy. The thermal response of the feet of diabetic patients following cold stimulus is captured using an infrared camera. The plantar foot in the images from a thermal video are segmented and registered for tracking points or specific regions. The temperature recovery of each point on the plantar foot is extracted using our bio-thermal model and analyzed. The regions that exhibit abnormal ability to recover are automatically identified to aid the physicians to recognize problematic areas. The key to our CAD system is the segmentation of infrared video. The main challenges for segmenting infrared video compared to normal digital video are (1) as the foot warms up, it also warms up the surrounding, creating an ever changing contrast; and (2) there may be significant motion during imaging. To overcome this, a hybrid segmentation algorithm was developed based on a number of techniques such as continuous max-flow, model based segmentation, shape preservation, convex hull, and temperature normalization. Verifications of the automatic segmentation and registration using manual segmentation and markers show good agreement.

The enzyme neuropathy target esterase (NTE) is present in neurons and deacylates the major membrane phospholipid, phosphatidylcholine (PtdCho). Mutation of the NTE gene or poisoning by neuropathic organophosphates—chemical inhibitors of NTE—causes distal degeneration of long spinal axons in humans. However, analogous neuropathological changes have not been reported in nestin-cre:NTEfl/fl mice with NTE-deficient neural tissue. Furthermore, altered PtdCho homeostasis has not been detected in NTE-deficient vertebrates. Here, we describe distal degeneration of the longest spinal axons in ?3-week-old nestin-cre:NTEfl/fl mice and in adult C57BL/6J mice after acute dosing with a neuropathic organophosphate: in both groups early degenerative lesions were followed by swellings comprising accumulated axoplasmic material. In mice dosed acutely with organophosphate, maximal numbers of lesions, in the longest spinal sensory axon tract, were attained within days and were preceded by a transient rise in neural PtdCho. In nestin-cre:NTEfl/fl mice, sustained elevation of PtdCho over many months was accompanied by progressive degeneration and massive swelling of axons in sensory and motor spinal tracts and by increasing hindlimb dysfunction. Axonal lesion distribution closely resembled that in hereditary spastic paraplegia (HSP). The importance of defective membrane trafficking in HSP and the association of NTE with the endoplasmic reticulum—the starting point for the constitutive secretory pathway and transport of neuronal materials into axons—prompted investigation for a role of NTE in secretion. Cultured NTE-deficient neurons displayed modestly impaired secretion, consistent with neuronal viability and damage in vivo initially restricted to distal parts of the longest axons. PMID:19759306

Skin biopsy has gained widespread use for the diagnosis of somatic small-fiber neuropathy, but it also provides information on sympathetic fiber morphology. We aimed to ascertain the diagnostic accuracy of skin biopsy in disclosing sympathetic nerve abnormalities in patients with autonomic neuropathy. Peripheral nerve fiber autonomic involvement was confirmed by routine autonomic laboratory test abnormalities. Punch skin biopsies were taken from the thigh and lower leg of 28 patients with various types of autonomic neuropathy for quantitative evaluation of skin autonomic innervation. Results were compared with scores obtained from 32 age-matched healthy controls and 25 patients with somatic neuropathy. The autonomic cutoff score was calculated using the receiver operating characteristic curve analysis. Skin biopsy disclosed a significant autonomic innervation decrease in autonomic neuropathy patients versus controls and somatic neuropathy patients. Autonomic innervation density was abnormal in 96% of patients in the lower leg and in 79% of patients in the thigh. The abnormal findings disclosed by routine autonomic tests ranged from 48% to 82%. These data indicate the high sensitivity and specificity of skin biopsy in detecting sympathetic abnormalities; this method should be useful for the diagnosis of autonomic neuropathy, together with currently available routine autonomic testing. PMID:23037327

The mechanism of the cranial neuropathy associated with heavy exposure to trichloroethylene (or dichloroethylene) is unknown. In severe cases there is destructive spread of the neuropathic process from the Vth cranial nerve nuclei up and down the brain stem in a manner that is difficult to explain on accepted neurotoxicological principles. However, there is a close association reported of this form of trigeminal neuropathy with reactivation of orofacial herpes simplex that suggests the possibility that the chemical, which readily gains entrance into the nervous system, may be responsible for reactivating the latent virus. This novel hypothesis is discussed in the light of current understanding of latency in herpes simplex infection in nervous tissue. PMID:2538571

Vitamin B(12) deficiency causes a wide range of hematological, gastrointestinal, and neurological manifestations. The most common neurological complication is subacute combined degeneration, sometimes associated with polyneuropathy. Isolated peripheral neuropathy due to cyanocobalamin deficiency is less frequent, and thus it may be overlooked. We describe 2 patients with isolated sensory axonal neuropathy secondary to vitamin B(12) deficiency who had complete clinical and electrophysiological recovery after cyanocobalamin replacement. Testing for serum vitamin B(12) and its metabolites should be done in any distal symmetric neuropathy. PMID:22334179

The dose limiting toxicity of the nitroimidazole radiosensitizers is peripherial neuropathy. Improved pharmacology of newer drugs has eliminated the encephalopathy. Peripheral neuropathies are predominently mild to moderate paresthesias of both hands and feet. Subjective changes occur with or without minimal objective changes on neurologic exam. All of the neuropathies occurred within 30 days of the last drug dose and are of varible duration. Sural nerve biopsies from patients indicate progressive axonal degeneration affecting both large and small caliber myelinated fibers. Axonal damage appears to be more severe in the distal portion of the nerves. More data are needed for correlation of clinical and pathological changes.

Difficulty in walking is seen in many people with peripheral neuropathies, but walking ability is not comprehensively measured by commonly used outcome measures. The clinimetric properties of the 12?Item Multiple Sclerosis Walking Scale (MSWS?12, renamed the Walk?12) were investigated in 65 patients with peripheral neuropathies. Owing to its excellent internal consistency and reliability, and strong correlation with measures of physical and social function (r>0.8), the Walk?12 is recommended for measuring walking ability in peripheral neuropathies. PMID:16574732

More than 30 genetic causes have been identified for the inherited neuropathies collectively referred to as Charcot-Marie-Tooth (CMT) disease. Previous therapies for CMT were limited to traditional approaches such as rehabilitation medicine, ambulation aids, and pain management. Identification of the genes causing CMT has led to improved genetic counseling and assistance in family planning. Identification of these genes is beginning to delineate common molecular pathways in multiple forms of CMT that can be exploited in future molecular therapies. Scientifically based clinical trials for CMT are currently being implemented. Techniques of gene therapy are advancing to the point that they may become feasible options for patients with CMT and other neurodegenerative diseases. PMID:16775380

Peripheral neuropathies are among the most common neurological diseases and have numerous causes, including diabetes, alcohol, hereditary, toxic, metabolic, infectious, inflammatory, ischaemic and paraneoplastic. Often, however, no definitive cause is identified and the condition is termed idiopathic neuropathy. Here we describe a patient who was initially diagnosed with idiopathic sciatic neuropathy but who was eventually diagnosed with prostate cancer. This is an uncommon manifestation of prostate cancer, and the diagnostic was difficult because prostate-specific antigen (PSA) was normal and the positron emission tomography scan negative. Changes in PSA should always raise the suspicion of prostate cancer, just as idiopathic progressive neuropathy should always raise the suspicion of an underlying malignancy, even when standard diagnostics fail to explain the patient's symptoms.

Clinical and pathological findings in leprosy are determined by the natural host immune response to Mycobacterium leprae. We previously described cases of painful neuropathy (PN) with no concurrent cause apart from a past history of leprosy successfully treated. Four leprosy previously treated patients who developed a PN years after multidrug therapy (MDT) are reported. The mean patient age was 52.75 years (47-64). The mean time interval of the recent neuropathy from the previous MDT was 19 years (12-26). A painful multiplex neuritis or polyneuropathy were observed respectively in two cases. Electrophysiological studies disclosed a sensory axonal neuropathy in two cases. Microvasculitis with no bacilli was seen in nerve biopsy. Neuropathic symptoms were improved with prednisone. We consider these cases as being a leprosy late-onset neuropathy (LLON) form of presentation. A delayed immune reaction could explain the late appearance of LLON. PMID:22699535

??This study examined the association between neuropathy limitations and depression in chemotherapy patients currently on treatment with a taxane-based, platinum-based or plant alkaloid chemotherapy drug.… (more)

Summary Sensory evaluation of diabetic neuropathy was undertaken by a new technique for assessment of thermal sensitivity. The method is simple and reproducible, and the mean normal value of the lateral border of the foot was 6.0 °C (3.6–9.8 °C, 95% confidence limits). Four groups of patients with diabetic neuropathy were examined: 22 with neuropathic ulcers and\\/or Charcot joints (groups 1

Immune-mediated neuropathies represent a heterogeneous spectrum of peripheral nerve disorders that can be classified according to time course, predominant involvement of motor/sensory fibers, distribution of deficits and paraclinical parameters such as electrophysiology and serum antibodies. In the last few years, significant advances have been achieved in elucidating underlying pathomechanisms, which made it possible to identify potential therapeutic targets. In this review, we discuss the latest development in pathogenesis and treatment of immune-mediated neuropathies. PMID:21179533

Multifocal motor neuropathy (MMN) is an acquired disorder with onset in adulthood. The authors describe a patient with a slowly progressing distal upper limb motor neuropathy since age 6 years, in whom definite conduction blocks in upper limbs, outside common entrapment sites, and no sensory involvement were consistent with MMN. IV immunoglobulin treatment produced marked muscle strength improvement and conduction block disappearance. MMN diagnosis should also be considered in childhood. PMID:16567714

Many of the most effective anti-cancer drugs induce a dose-limiting peripheral neuropathy that compromises therapy. Evidence from animal models of chemotherapy-induced painful peripheral neuropathy produced by the taxane agent, paclitaxel, and the platinum-complex agent, oxaliplatin, indicate that they produce neuropathy via a common mechanism-a toxic effect on the mitochondria in primary afferent sensory neurons. Bortezomib is from the proteasome-inhibitor class of chemotherapeutics. It also produces a dose-limiting peripheral neuropathy, but its effects on neuronal mitochondria are unknown. To investigate this, we developed a model of bortezomib-induced painful peripheral neuropathy in the rat and assessed mitochondrial function (respiration and ATP production) in sciatic nerve samples harvested at two time points: day 7, which is three days after treatment and before pain appears, and day 35, which is one month post-treatment and the time of peak pain severity. We found significant deficits in Complex I-mediated and Complex II-mediated respiration, and in ATP production at both time points. Prophylactic treatment with acetyl-L-carnitine, which has previously been shown to prevent paclitaxel- and oxaliplatin-induced mitochondrial dysfunction and pain, completely blocked bortezomib's effects on mitochondria and pain. These results suggest that mitotoxicity may be the core pathology for all chemotherapy-induced peripheral neuropathy and that drugs that protect mitochondrial function may be useful chemotherapy adjuncts. PMID:22947198

During 1992-1993, an epidemic of neurologic disease in Cuba affected 50,862 patients with opticneuropathy, sensorineural deafness, predominantly sensory peripheral neuropathy, and dorsolateral myelopathy. The clinical syndromes were identical to those of prisoners of war subjected to nutritional restriction in tropical prison camps during World War II (Strachan's disease). A dietary deficiency of group B vitamins and sulfur-containing amino acids appears to have been the primary cause of the epidemic. This was a consequence of economic and political events in Cuba linked to the collapse of the Soviet Union and socialist countries. The recently toughened 30-year-old US economic embargo on Cuba contributed to these problems and hampered the investigation, treatment, and prevention of the epidemic. A plea is made to the neurologic community to request the lifting of the trade blockade on a humanitarian basis. PMID:7936221

We report a case of Western type hairy cell leukemia (HCL), a very rare leukemia in Japan. In this malignancy, leukemic cells in a peripheral blood film may be missed due in part to accompanying pancytopenia and in part to loss of typical cytoplasmic projections if prepared in a conventional Japanese way using forced air-drying. Our present patient also had a variety of autoantibodies and the clinical picture was primarily that of Evans syndrome (ES), suggesting disturbed immune responses associated with the HCL. Although HCL accompanied by either AIHA or ITP has been reported, the occurrence of ES in HCL is extremely rare. PMID:24850460

A 69-year-old woman presented 2 days after painless visual loss of her left eye, which developed over 45 min. She was otherwise systemically well. Twelve weeks prior, she had left-sided frontotemporal headache which lasted for 8 weeks. Examination showed left visual acuity to perception of hand movement only and a relative afferent pupillary defect; her fundi looked normal. The rest

Methylene blue (MB) is a diaminophenothiazine with potent antioxidant and unique redox properties that prevent morphologic\\u000a degenerative changes in the mouse retina induced by rotenone, a specific mitochondrial complex I inhibitor. This study evaluated\\u000a pigmented rats to determine whether MB’s neuroprotective effects against rotenone-mediated retinal neurotoxicity have functional\\u000a relevance and whether these effects are mediated by an improvement in neuronal

Background Suprascapular neuropathy (SSN) is generally thought of as a diagnosis of exclusion. However, increasing attention is being paid to the diagnosis, treatment and rehabilitation of this pathology to prevent chronic supraspinatus and infraspinatus atrophy in patients. To date, literature has only articulated variable or customized treatment and rehabilitation plans without clear standardized care. This case study provides a detailed description of the diagnosis, treatment, and rehabilitation of a collegiate baseball player's recovery from suprascapular nerve release. Case Presentation A 20 year-old male baseball pitcher with right shoulder pain reported for athletic training evaluation, was treated conservatively, and due to lack of resolution was referred for further imaging and evaluation by an orthopedist. Following inconclusive magnetic resonance imaging findings the patient underwent electrodiagnostic testing which showed decreased nerve conduction velocity of the right suprascapular nerve. The patient elected for surgical intervention. Post-operative rehabilitation followed and the patient was able to pitch in 22 weeks. The patient provided positive subjective feedback and was able to return to unrestricted pitching without pain, loss of velocity, or loss in pitch control. Conclusion This study demonstrates a need for further investigation into the most appropriate treatment and rehabilitation of suprascapular nerve injury. PMID:23785580

Diabetic neuropathy (DN) is a widespread disabling disorder comprising peripheral nerves' damage. DN develops on a background of hyperglycemia and an entangled metabolic imbalance, mainly oxidative stress. The majority of related pathways like polyol, advanced glycation end products, poly-ADP-ribose polymerase, hexosamine, and protein kinase c all originated from initial oxidative stress. To date, no absolute cure for DN has been defined; although some drugs are conventionally used, much more can be found if all pathophysiological links with oxidative stress would be taken into account. In this paper, although current therapies for DN have been reviewed, we have mainly focused on the links between DN and oxidative stress and therapies on the horizon, such as inhibitors of protein kinase C, aldose reductase, and advanced glycation. With reference to oxidative stress and the related pathways, the following new drugs are under study such as taurine, acetyl-L-carnitine, alpha lipoic acid, protein kinase C inhibitor (ruboxistaurin), aldose reductase inhibitors (fidarestat, epalrestat, ranirestat), advanced glycation end product inhibitors (benfotiamine, aspirin, aminoguanidine), the hexosamine pathway inhibitor (benfotiamine), inhibitor of poly ADP-ribose polymerase (nicotinamide), and angiotensin-converting enzyme inhibitor (trandolapril). The development of modern drugs to treat DN is a real challenge and needs intensive long-term comparative trials. PMID:23738033

Note There is now an accompanying numpy tutorial. Matplotlib tutorial Nicolas P. Rougier Other Types of Plots Beyond this tutorial Quick references This tutorial is based on Mike MÃ¼ller's tutorial available from the scipy lecture notes. Sources are available here. Figures are in the figures

Aims/Introduction To elucidate the clinical significance of median neuropathy at the wrist (MN) in patients with diabetes. Materials and Methods In total, 340 patients with diabetes who were hospitalized for glycemic control were enrolled in the present study. The diagnoses of MN and diabetic polyneuropathy (DPN) were based on electrophysiological criteria. A total of 187 patients were divided into four subgroups: patients without MN or DPN; patients with MN without DPN; patients with MN and DPN; and patients with DPN without MN. Intergroup comparisons of clinical characteristics and results of nerve conduction studies were carried out. Results A total of 71 patients had neither MN nor DPN; 25 had MN, but no DPN; 55 had MN and DPN; and 36 had DPN, but no MN. In comparison with the MN and DPN group, the MN without DPN group included more patients in the early phase of diabetes (diagnosed within the past 5 years) and fewer patients with diabetic microangiopathy. Comparative median nerve conduction studies showed significantly lower motor and sensory nerve conduction velocities, longer F-wave latencies, and smaller sensory nerve action potentials in patients with MN and DPN than in those without DPN. Conclusions MN in patients with diabetes could be attributed to an impairment in axonal function at common entrapment sites, and could be used to identify an early manifestation of diabetic neuropathy.

Painful neuropathy is a common and often progressive complication of diabetes. Patients frequently report symptoms of tingling, burning, lancinating pain, hyperesthesia, and allodynia. The natural history of the disease may vary from intermittent mild symptoms to severe chronic daily pain; the latter is often associated with diminished quality of life. There are a variety of pharmaceutical agents from different medicinal categories available for the symptomatic treatment of painful diabetic neuropathy, however selecting an agent is often challenging given the breadth of choices and lack of consistent guidelines. As a result, many patients remain untreated or undertreated. This article presents a practical clinical approach to the treatment of pain in diabetic neuropathy. Recommendations for first-, second-, and third-line medications are based on specific evidence for the treatment of painful diabetic neuropathy as well as safety, tolerability, drug interactions, and cost. Additional topics of discussion include breakthrough pain, opioid use, and topical therapies. This review does not comprehensively discuss all possible treatments for painful neuropathy, but provides a systematic approach designed to guide clinicians in tailoring therapies to the individual patient. PMID:21709806

A prospective study of patients receiving cis-diaminedichloroplatin II (DDP) was carried out to determine if risk factors could be identified related to the patient's living habits or past medical history that would predict in which patients DDP neuropathy might develop. Sixty-nine patients receiving six different combinations of chemotherapeutic agents, including DDP were examined. Twenty-eight of these patients received DDP in combination with the radioprotective agent S-2-(3-aminopropylamino)-ethylphosporothioic acid (WR 2721). No risk factors were identified relating to personal habits or past medical history of the patients. However, patients receiving DDP (40 mg/m2) on 5 consecutive days had a significantly higher incidence of neuropathy. Patients receiving DDP in combination with WR 2721 had a significantly lower incidence of neuropathy, and the mean dose at onset was significantly higher than the mean dose at onset of neuropathy for all other groups. In addition, five of six patients who were available for long-term follow-up demonstrated nearly complete reversal of the signs and symptoms of neuropathy.

Objective To demonstrate the prevalence and characteristics of subclinical ulnar neuropathy at the elbow in diabetic patients. Methods One hundred and five patients with diabetes mellitus were recruited for the study of ulnar nerve conduction analysis. Clinical and demographic characteristics were assessed. Electrodiagnosis of ulnar neuropathy at the elbow was based on the criteria of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM1 and AANEM2). The inching test of the ulnar motor nerve was additionally performed to localize the lesion. Results The duration of diabetes, the existence of diabetic polyneuropathy (DPN) symptoms, the duration of symptoms, and HbA1C showed significantly larger values in the DPN group (p<0.05). Ulnar neuropathy at the elbow was more common in the DPN group. There was a statistically significant difference in the number of cases that met the three diagnostic criteria between the no DPN group and the DPN group. The most common location for ulnar mononeuropathy at the elbow was the retrocondylar groove. Conclusion Ulnar neuropathy at the elbow is more common in patients with DPN. If the conduction velocities of both the elbow and forearm segments are decreased to less than 50 m/s, it may be useful to apply the AANEM2 criteria and inching test to diagnose ulnar neuropathy. PMID:24639928

Background Present study investigated the relationship between speech identification scores in quiet and parameters of cortical potentials (latency of P1, N1, and P2; and amplitude of N1/P2) in individuals with auditory neuropathy. Methods Ten individuals with auditory neuropathy (five males and five females) and ten individuals with normal hearing in the age range of 12 to 39 yr participated in the study. Speech identification ability was assessed for bi-syllabic words and cortical potentials were recorded for click stimuli. Results Results revealed that in individuals with auditory neuropathy, speech identification scores were significantly poorer than that of individuals with normal hearing. Individuals with auditory neuropathy were further classified into two groups, Good Performers and Poor Performers based on their speech identification scores. It was observed that the mean amplitude of N1/P2 of Poor Performers was significantly lower than that of Good Performers and those with normal hearing. There was no significant effect of group on the latency of the peaks. Speech identification scores showed a good correlation with the amplitude of cortical potentials (N1/P2 complex) but did not show a significant correlation with the latency of cortical potentials. Conclusion Results of the present study suggests that measuring the cortical potentials may offer a means for predicting perceptual skills in individuals with auditory neuropathy. PMID:18377641

Chronic alcohol consumption produces painful peripheral neuropathy for which there is no reliable successful therapy, mainly due to lack of understanding of its pathobiology. Alcoholic neuropathy involves coasting caused by damage to nerves that results from long term excessive drinking of alcohol and is characterized by spontaneous burning pain, hyperalgesia and allodynia. The mechanism behind alcoholic neuropathy is not well understood, but several explanations have been proposed. These include activation of spinal cord microglia after chronic alcohol consumption, oxidative stress leading to free radical damage to nerves, activation of mGlu5 receptors in the spinal cord and activation of the sympathoadrenal and hypothalamo-pituitary-adrenal (HPA) axis. Nutritional deficiency (especially thiamine deficiency) and/or the direct toxic effect of alcohol or both have also been implicated in alcohol-induced neuropathic pain. Treatment is directed towards halting further damage to the peripheral nerves and restoring their normal functioning. This can be achieved by alcohol abstinence and a nutritionally balanced diet supplemented by all B vitamins. However, in the setting of ongoing alcohol use, vitamin supplementation alone has not been convincingly shown to be sufficient for improvement in most patients. The present review is focused around the multiple pathways involved in the development of peripheral neuropathy associated with chronic alcohol intake and the different therapeutic agents which may find a place in the therapeutic armamentarium for both prevention and management of alcoholic neuropathy. PMID:21988193

nondiabetic mice that exhibit mechanical hyperalgesia and thermal hypoalgesia are also being utilized to model neuropathy in pre-diabetes [5, 23, 30]. It should be noted that the neuronal cell bodies of the axons that innervate the lower limbs and hind paws... determine diabetic neuropathy progression and phenotype. Rodent Models of Diabetic Neuropathy Numerous diabetic rodent models have been developed to study diabetic neuropathy. Type 1 diabetes is primarily induced in mice or rats by intra...

Preceding the joint meeting of the 19th annual Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes (NEURODIAB) and the 8th International Symposium on Diabetic Neuropathy in Toronto, Canada, 13–18 October 2009, expert panels were convened to provide updates on classification, definitions, diagnostic criteria, and treatments of diabetic peripheral neuropathies (DPNs), autonomic neuropathy, painful DPNs, and structural alterations in DPNs. PMID:20876709

Soluble Epoxide Hydrolase Inhibition Is Antinociceptive in a Mouse Model of Diabetic Neuropathy clinical need. This need is becoming urgent as the diabetic population increases worldwide and neuropathy occurs in 1 of every 2 patients.8,12 The pain of diabetic neuropathy is due to nerve damage

The immediate heart-rate response to standing was measured in 22 normal controls and 25 patients with diabetes, 15 of whom had autonomic neuropathy. The response in the controls and patients without autonomic neuropathy was characteristic and consistent, with tachycardia maximal at around the 15th beat and relative bradycardia maximal at around the 30th beat. The diabetics with autonomic neuropathy, however,

In the second part of this review we deal with the clinical aspects of immune-mediated demyelinating neuropathies. We describe the relationship between pathophysiology and symptoms and discuss the pathophysiology of specific disease entities, including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, anti-myelin-associated glycoprotein neuropathy, and POEMS syndrome. PMID:24037667

NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy. The discussion was divided into five areas: (1) status of commonly used rodent models of diabetes, (2) nerve structure, (3) electrophysiological assessments of nerve function, (4) behavioral assessments of nerve function, and (5) the role of biomarkers in disease phenotyping. Participants discussed the current understanding of each area, gold standards (if applicable) for assessments of function, improvements of existing techniques, and utility of known and exploratory biomarkers. The research opportunities in each area were outlined, providing a possible roadmap for future studies. The meeting concluded with a discussion on the merits and limitations of a unified approach to phenotyping rodent models of diabetic neuropathy and a consensus formed on the definition of the minimum criteria required for establishing the presence of the disease. A neuropathy phenotype in rodents was defined as the presence of statistically different values between diabetic and control animals in 2 of 3 assessments (nocifensive behavior, nerve conduction velocities, or nerve structure). The participants propose that this framework would allow different research groups to compare and share data, with an emphasis on data targeted toward the therapeutic efficacy of drug interventions. PMID:24934510

Auditory neuropathy/dys-synchrony is a form of hearing impairment in which cochlear outer hair cell function is spared but neural transmission in the auditory pathway is disordered. This condition, or group of conditions with a common physiologic profile, accounts for approximately 7% of permanent childhood hearing loss and a significant (but as yet undetermined) proportion of adult impairment. This paper presents an overview of the mechanisms underlying auditory neuropathy/dys-synchrony-type hearing loss and the clinical profile for affected patients. In particular it examines the perceptual consequences of auditory neuropathy/dys-synchrony, which are quite different from those associated with sensorineural hearing loss, and considers currently available, and future management options. PMID:15920648

A relationship has been reported by several research groups [1 - 4] between the density and shapes of nerve fibers in the cornea and the existence and severity of peripheral neuropathy. Peripheral neuropathy is a complication of several prevalent diseases or conditions, which include diabetes, HIV, prolonged alcohol overconsumption and aging. A common clinical technique for confirming the condition is intramuscular electromyography (EMG), which is invasive, so a noninvasive technique like the one proposed here carries important potential advantages for the physician and patient. A software program that automatically detects the nerve fibers, counts them and measures their shapes is being developed and tested. Tests were carried out with a database of subjects with levels of severity of diabetic neuropathy as determined by EMG testing. Results from this testing, that include a linear regression analysis are shown.

Pain is a frequent debilitating feature reported in peripheral neuropathies with involvement of small nerve (A? and C) fibers. Voltage-gated sodium channels are responsible for the generation and conduction of action potentials in the peripheral nociceptive neuronal pathway where NaV 1.7, NaV 1.8, and NaV 1.9 sodium channels (encoded by SCN9A, SCN10A, and SCN11A) are preferentially expressed. The human genetic pain conditions inherited erythromelalgia and paroxysmal extreme pain disorder were the first to be linked to gain-of-function SCN9A mutations. Recent studies have expanded this spectrum with gain-of-function SCN9A mutations in patients with small fiber neuropathy and in a new syndrome of pain, dysautonomia, and small hands and small feet (acromesomelia). In addition, painful neuropathies have been recently linked to SCN10A mutations. Patch-clamp studies have shown that the effect of SCN9A mutations is dependent upon the cell-type background. The functional effects of a mutation in dorsal root ganglion (DRG) neurons and sympathetic neuron cells may differ per mutation, reflecting the pattern of expression of autonomic symptoms in patients with painful neuropathies who carry the mutation in question. Peripheral neuropathies may not always be length-dependent, as demonstrated in patients with initial facial and scalp pain symptoms with SCN9A mutations showing hyperexcitability in both trigeminal ganglion and DRG neurons. There is some evidence suggesting that gain-of-function SCN9A mutations can lead to degeneration of peripheral axons. This review will focus on the emerging role of sodium channelopathies in painful peripheral neuropathies, which could serve as a basis for novel therapeutic strategies. PMID:25250524

Ganglions of the wrist and hand causing compressive neuropathies are rare clinical entities. Compression of the ulnar and median nerves in their respective fibro-osseous tunnels lead to characteristic patterns of motor and/or sensory deficits, which are directly related to the location of the lesion. We present a unique case of a "dumbbell" shaped ganglion invading both Guyon's canal and the carpal tunnel causing a dual compressive neuropathy of the ulnar and median nerve. We discuss the patho-anatomy, clinical assessment, investigation and surgical treatment of this condition. PMID:24641752

An AIDS physician at New York's St. Vincent's Hospital reports considerable success with a topical formulation of the prescription drug Voltaren (a non-steroidal anti-inflammatory in the same class as Advil or Aleve). Dr. David Kaufman found the drug reduces pain and has essentially no side effects. The topical formulation, called Emulgel, is not sold in the United States. Information is requested about results using Emulgel and other brands of topical diclofenac sodium for treating neuropathy. Readers are also asked to share experiences with topical use of other anti-inflammatory drugs for relieving neuropathy. Contact information is provided. PMID:11366714

Dogs exposed to acrylamide develop a sensorimotor peripheral neuropathy and megaoesophagus. The presence of neuropathy was confirmed electrophysiologically and histologically. Hindlimb motor conduction velocity was reduced and there was a loss of large diameter myelinated fibres in the dorsal common digital nerve and the tibial nerve. The conduction velocity of vagal motor fibres innervating the thoracic oesophagus was not decreased; there was a reduction in the conduction velocity of the mixed nerve action potential of the vagus. Degenerating nerve fibres were observed in the vagus in the midthoracic region. The damage to vagal nerve fibres may be an important factor in the causation of megaoesophagus. Images PMID:6288880

Abstract: Intravenous immunoglobulins (IVIg) have been shown in a number of trials, to be an effective treatment for the three main types of inflammatory neuropathies: Guillain-Barré Syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and multifocal motor neuropathy (MMN). IVIg is thought to exert its immunomodulatory effects by affecting several components of the immune system including B-cells, T-cells, macrophages, complement, cytokines and cellular adhesion molecules. This article reviews the published evidence and the principal postulated mechanisms of action of intravenous immunoglobulins with special emphasis on inflammatory neuropathies. Key Words: Intravenous immunoglobulins, mechanisms of action, inflammatory neuropathy, Guillain Barre syndrome, Chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy.

Diabetic peripheral and autonomic neuropathies are common complications of diabetes with broad spectrums of clinical manifestations and high morbidity. Studies using various agents to target the pathways implicated in the development and progression of diabetic neuropathy were promising in animal models. In humans, however, randomized controlled studies have failed to show efficacy on objective measures of neuropathy. The complex anatomy of the peripheral and autonomic nervous systems, the multitude of pathogenic mechanisms involved, and the lack of uniformity of neuropathy measures have likely contributed to these failures. To date, tight glycemic control is the only strategy convincingly shown to prevent or delay the development of neuropathy in patients with type 1 diabetes and to slow the progression of neuropathy in some patients with type 2 diabetes. Lessons learned about the role of glycemic control on distal symmetrical polyneuropathy and cardiovascular autonomic neuropathy are discussed in this review. PMID:25139473

Almitrine bismesylate is thought to cause sensory peripheral neuropathy. Forty-six patients are reported who received almitrine bismesylate alone for chronic respiratory failure or in combination with raubasine for various cerebrovascular diseases. Polyneuropathy appeared between 9 and 25 months after the onset of treatment. Sensory signs and symptoms were confined to the distal parts of the lower limbs and involved large

Recent progress in immunopathological studies of peripheral nerve and lymph node fragments together with 16 personal cases and numerous clinicopathological reports have suggested a new classification of peripheral neuropathies (PN) and lymphomas. These are: (1) PN due to local infiltrations by a T-cell lymphoma; (2) acute polyradiculoneuritis due to active demyelination and associated with infiltrates of a T-cell lymphoma in

Morphological findings in sural nerves were related to nerve conduction in 12 patients with diabetic neuropathy, five with mainly sensory involvement, four with severe, symmetrical sensory-motor polyneuropathy, and three with multiple mononeuropathy. All had loss of large and small myelinated and of unmyelinated fibres, even early in the disease; segmental remyelination was the most prominent myelin alteration in teased fibres,

Observations have been made on nine cases of painful diabetic neuropathy of acute onset. All cases were male and all were associated with and preceded by precipitous and severe weight loss. The pain was of a continuous burning quality and experienced mainly in the legs, especially distally. Contact discomfort of the skin was often a troublesome feature, but sensory loss

The incidence of antecedent events and serological evidence of preceding infection were studied in 100 patients with acute idiopathic neuropathy and age and sex matched control subjects in South-East England. Symptoms of respiratory infections occurred within one month before onset of neuropathic symptoms in 38% of patients and 12% of controls (p less than 0.001) and symptoms of gastrointestinal infections

Gastric acid output in response to insulin-induced hypoglycaemia and pentagastrin was measured in 18 diabetic patients with symptoms of autonomic neuropathy. Two patients had achlorhydria but the rest responded normally to pentagastrin. The acid output evoked by insulin-induced hypoglycaemia was low in 10 of the 16 patients who secreted acid in response to pentagastrin. These changes suggest that vagal impairment

Peripheral neuropathy (PN) is one of the most important complications of multiple myeloma (MM) treatment. PN can be caused by MM itself, either by the effects of the monoclonal protein or in the form of radiculopathy from direct compression, and particularly by certain therapies, including bortezomib, thalidomide, vinca alkaloids and cisplatin. Clinical evaluation has shown that up to 20% of

Oxygen free radical damage is regarded as a direct or indirect common pathway associated with diabetic neuropathy and is the main cause of complications in peripheral neuropathies. We speculate that Jiaweibugan decoction has a significant effect in treating diabetic peripheral neuropathy through an anti-oxidative stress pathway. In this study, a diabetic rat model was established by intraperitoneal injection of streptozotocin. Rats were treated with Jiaweibugan decoction via intragastric administration. The levels of malondialdehyde and glutathione, which are indirect indexes of oxidative stress, in serum were determined using a colorimetric method. The expression levels of nuclear factor kappa B p65 mRNA and p38 mitogen-activated protein kinase, which are oxidative stress associated factors, in the dorsal root ganglion of spinal S4–6 segments were evaluated by reverse-transcriptase polymerase chain reaction and immunohistochemistry. Results showed that, Jiaweibugan decoction significantly ameliorated motor nerve conduction velocity in diabetic rats, effectively decreased malondialdehyde levels in serum and the expression of nuclear factor kappa B p65 mRNA and p38 mitogen-activated protein kinase mRNA in the dorsal root ganglion, and increased glutathione levels in serum. Therefore, our experimental findings indicate that Jiaweibugan decoction plays an anti-oxidative stress role in the diabetic peripheral neuropathy process, which has a protective effect on peripheral nerve injury.

To investigate the pathophysiology of faecal incontinence in diabetes mellitus, two groups of diabetic patients were studied: 14 subjects (7 females and 7 males, mean age 57 +/- 9 years) with faecal incontinence (Group A) and 15 subjects (6 females and 9 males, mean age 54.7 +/- 8 years) without faecal incontinence but affected by somatic peripheral neuropathy. A third group (C) of 10 healthy volunteers was used as controls. All subjects underwent electroneurographic evaluation of peripheral neuropathy, pudendal nerve terminal motor latency, anorectal manometry and rectal sensitivity tests. All the patients of group A had somatic peripheral neuropathy. Maximum squeeze pressure was lower in A compared to C (P < 0.025) and sustained for a shorter period in A compared with B (P < 0.0005) and C (P < 0.0005). All rectal sensitivity thresholds were higher in A compared with B and C. Pudendal Nerve Terminal Motor Latency was prolonged in 93% of patients studied in group A and in 73% of patients in group B (A vs B P < 0.005), with a significant difference in comparison with C: A vs C P < 0.0005, B vs C P < 0.005. Our findings suggest that somatic neuropathy plays an important role in faecal incontinence in diabetic patients, combined with sensation threshold impairment as a feature of an autonomic involvement. PMID:8064189

MENU Return to Web version Diabetic Neuropathy | What is a Total Contact Cast? What is a total contact cast? A total contact cast is a cast used to treat ulcers (serious, deep sores) on a person’s foot. It consists of a fiberglass shell that fits around your leg and foot very ...

Here we describe the imaging findings in a 73-year-old woman who had pain in the right inguinal region, followed by progressive weakness of muscles innervated by the right femoral and obturator nerves, diagnosed as nondiabetic lumbosacral radiculoplexus neuropathy. Magnetic resonance neurography showed thickening and increase in signal intensity of the right femoral and obturator nerves. PMID:23750469

Peripheral neuropathies are a common side effect of certain types of chemotherapy drugs, including taxanes, platinum-based drugs, vinca alkaloids, and thalidomide. Neuropathies may last for months or years following treatment and can impact functional performance and quality of life. The purpose of this study was to explore the effects of chemotherapy-induced peripheral neuropathy (CIPN) and neuropathic pain on the lives of patients with cancer. Participants were recruited from an urban outpatient medical oncology clinic in West Central Florida. Semistructured, private interviews with 14 participants were conducted and transcripts were reviewed for symptoms and effects. Participants often had difficulty describing neuropathic symptoms but reported simultaneous pain or discomfort and loss of sensation in the upper and lower extremities. Injuries secondary to numbness, muscle weakness, and loss of balance were reported. Neuropathic symptoms interfered with many aspects of daily life and participants voiced feelings of frustration, depression, and loss of purpose as a result of having to give up enjoyable activities. The results of this study emphasize the importance of ongoing assessment and communication with patients about their experiences with peripheral neuropathies. Knowledge of what patients with CIPN experience will guide nurses in suggesting interventions to promote safety and help alleviate symptoms. PMID:20529785

Nerve growth factor (NGF) reverses some effects of axotomy and prevents toxic neuropathy in adult rodents. We tested the effect of NGF on behavioral hyperalgesia resulting from a chronic constriction injury (CCI) of the sciatic nerve in the rat [5]. CCI rats exhibit thermal hyperalgesia as demonstrated by a reduction of paw withdrawal latency to a noxious thermal stimulus applied

Six families are described with hereditary motor and sensory neuropathy (HMSN) of probable autosomal recessive inheritance. Four of these were classified as HMSN type I and two as type II. The consanguinity rate in this series was high, suggesting that these recessive genes are rare. In comparison with the dominantly inherited forms of these disorders, the mean age of onset

The author discusses several ways in which participation in clinical research on neuropathies can be improved. Both patients and providers need to become better informed about the availability of trials. Patient advocacy groups and professional organizations should play a major role in informing their constituents about the value of clinical research and assist patients and providers in becoming involved.

AIMTo prevent scarring after surgical optic nerve sheath decompression, it has been suggested that treating the area of fenestration with mitomycin C (MMC) might be effective. An animal model was used to test whether this toxic substance may cause opticneuropathy.METHODSThe optic nerves of 15 rabbits were exposed to balanced salt solution (BSS) or mitomycin C (MMC) in a concentration

Neurotrophic factors may play key roles in pathophysiological mechanisms of human neuropathies. Nerve growth factor (NGF) is trophic to small-diameter sensory fibers and regulates nociception. This review focuses on sensory dysfunction and the potential of neurotrophic treatments. Genetic neuropathy. Mutations of the NGF high-affinity receptor tyrosine kinase A (Trk A) have been found in congenital insensitivity to pain and anhidrosis; these are likely to be partial loss-of-function mutations, as axon-reflex vasodilatation and sweating can be elicited albeit reduced, suggesting rhNGF could restore nociception in some patients. Leprous neuropathy. Decreased NGF in leprosy skin may explain cutaneous hypoalgesia even with inflammation and rhNGF may restore sensation, as spared nerve fibers show Trk A-staining. Diabetic neuropathy. NGF is depleted in early human diabetic neuropathy skin, in correlation with dysfunction of nociceptor fibers. We proposed rhNGF prophylaxis may prevent diabetic foot ulceration. Clinical trials have been disappointed, probably related to difficulty delivering adequate doses and need for multiple trophic factors. NGF and glial cell line-derived neurotrophic factor (GDNF) are both produced by basal keratinocytes and neurotrophin (NT-3) by suprabasal keratinocytes: relative mRNA expression was significantly lower in early diabetic neuropathy skin compared to controls, for NGF (P < 0.02), BDNF (P < 0.05), NT-3 (P < 0.05), GDNF (< 0.02), but not NT4/5, Trk A or p75 neurotrophin receptor (all P > 0.05). Posttranslational modifications of mature and pro-NGF may also affect bioactivity and immunoreactivity. A 53 kD band that could correspond to a prepro-NGF-like molecule was reduced in diabetic skin. Traumatic neuropathy and pain. While NGF levels are acutely reduced in injured nerve trunks, neuropathic patients with chronic skin hyperalgesia and allodynia show marked local increases of NGF levels; here anti-NGF agents may provide analgesia. Physiological combinations of NGF, NT-3 and GDNF, to mimic a 'surrogate target organ', may provide a novel 'homeostatic' approach to prevent the development and ameliorate intractable neuropathic pain (e.g., at painful amputation stumps). PMID:14699981

Many studies have shown that a mechanical displacement of the axonal membrane accompanies the electrical pulse defining the Action Potential (AP). Despite a large and diverse body of experimental evidence, there is no theoretical consensus either for the physical basis of this mechanical wave nor its interdependence with the electrical signal. In this manuscript we present a model for these mechanical displacements as arising from the driving of surface wave modes in which potential energy is stored in elastic properties of the neuronal membrane and cytoskeleton while kinetic energy is carried by the axoplasmic fluid. In our model these surface waves are driven by the traveling wave of electrical depolarization that characterizes the AP, altering the compressive electrostatic forces across the membrane as it passes. This driving leads to co-propagating mechanical displacements, which we term Action Waves (AWs). Our model for these AWs allows us to predict, in terms of elastic constants, axon radius and axoplasmic density and viscosity, the shape of the AW that should accompany any traveling wave of voltage, including the AP predicted by the Hodgkin and Huxley (HH) equations. We show that our model makes predictions that are in agreement with results in experimental systems including the garfish olfactory nerve and the squid giant axon. We expect our model to serve as a framework for understanding the physical origins and possible functional roles of these AWs in neurobiology.

Background: Giant axonal neuropathy (GAN) is a severe recessive disorder characterised by variable combination of progressive sensory motor neuropathy, central nervous system (CNS) involvement, and "frizzly" hair. The disease is caused by GAN gene mutations on chromosome 16q24.1. Aims: To search for GAN gene mutations in Turkish patients with GAN and characterise the phenotype associated with them. Methods: Linkage and mutation analyses were performed in six affected patients from three consanguineous families. These patients were also investigated by cranial magnetic resonance imaging (MRI) and electroencephalography (EEG). Electromyography (EMG) was performed in heterozygous carriers from family 1 and family 3. Results: Linkage to 16q24.1 was confirmed by haplotype analysis. GAN mutations were identified in all families. Family 1 had the R293X mutation, previously reported in another Turkish family. Families 2 and 3, originating from close geographical areas, shared a novel mutation, 1502+1G>T, at the donor splice site of exon 9. All patients displayed a common phenotype, including peripheral neuropathy, cerebellar ataxia, and frizzly hair. Cranial MRI showed diffuse white matter abnormalities in two patients from family 1 and the patient from family 3, and minimal white matter involvement in the patient from family 2. EMG of a heterozygous R293X mutation carrier showed signs of mild axonal neuropathy, whereas a 1502+1G>T mutation carrier had normal EMG. EEG abnormalities were found in three patients. Conclusion: These findings highlight the association of CNS involvement, in particular white matter abnormalities, with peripheral neuropathy in GAN. The phenotypical consequences of both mutations (when homozygous) were similar. PMID:15897506

The mechanism/s leading to diabetic neuropathy are complex. Transforming growth factor-?1 (TGF-?1) has been associated with diabetic nephropathy and retinopathy but not neuropathy. In this study, changes in TGF-? isoforms were examined in-vivo and in-vitro. Two groups of animals, streptozotocin diabetic with neuropathy and non-diabetic controls were examined at 4 weeks (n=10/group) and 12 weeks (n=8/group). In diabetic DRG using quantitative real-time PCR (QRT-PCR), TGF-?1 and TGF-?2 mRNA, but not TGF-?3, was increased at 4 and 12 weeks. In sciatic nerve TGF-?3 mRNA was primarily increased. Immunohistochemistry (DRG) and immunoblotting (sciatic nerve) showed similar differential protein expression. In sciatic nerve TGF-? formed homo- and heterodimers, of which ?2/?3, ?1/?1, and ?1/?3 were significantly increased, while that of the TGF-?2/?2 homodimer was decreased, in diabetic compared to non-diabetic rats. In-vitro, pretreatment of embryonic DRG with TGF-? neutralizing antibody prevents the increase in total TGF-? protein observed with high glucose using immunoblotting. In high glucose conditions, combination with TGF-?2 > ?1 increases the percent of cleaved caspase-3 compared to high glucose alone and TGF-? neutralizing antibody inhibits this increase. Furthermore, consistent with the findings in diabetic DRG and nerve, TGF-? isoforms applied directly in vitro reduce neurite outgrowth, and this effect is partially reversed by TGF-? neutralizing antibody. These findings implicate upregulation of TGF-? in experimental diabetic peripheral neuropathy and indicate a novel mechanism of cellular injury related to elevated glucose levels. In combination, these findings indicate a potential new target for treatment of diabetic peripheral neuropathy. PMID:18406405

A brief historical and descriptive account of solid injection is followed by a detailed review of the available theoretical and experimental data that seem to throw light on the mechanism of this form of atomization. It is concluded that this evidence indicates that (1) the atomization accompanying solid injection occurs at the surface of the liquid after it issues as a solid stream from the orifice; and (2) that such atomization has a mechanism physically identical with the atomization which takes place in an air stream, both being due merely to the formation, at the gas-liquid interface, of fine ligaments under the influence of the relative motion of gas and liquid, and to their collapse, under the influence of surface tension, to form the drops in the spray.

Although most of sacral perineural cysts are asymptomatic, some may produce symptoms. Specific radicular pain may be due to distortion, compression, or stretching of nerve root by a space occupying cyst. We report a rare case of S1 radiculopathy caused by sacral perineural cyst accompanying disc herniation. The patient underwent a microscopic discectomy at L5-S1 level. However, the patient's symptoms did not improved. The hypesthesia persisted, as did the right leg pain. Cyst-subarachnoid shunt was set to decompress nerve root and to equalize the cerebrospinal fluid pressure between the cephalad thecal sac and cyst. Immediately after surgery, the patient had no leg pain. After 6 months, the patient still remained free of leg pain. PMID:19352483

In parallel with a long history of inquiry into action potential (AP) propagation, many studies have shown that a mechanical displacement of the axonal membrane accompanies the well characterized electrical pulse. Despite a large and diverse body of experimental evidence, there is no theoretical consensus either for the physical basis for this mechanical wave nor its interdependence with the electrical signal. In this manuscript we present a model for these mechanical displacements as arising from the driving of surface wave modes in which potential energy is stored in elastic properties of the neuronal membrane and cytoskeleton while kinetic energy is stored in the movement of the axoplasmic fluid. In our model these surface waves are driven by the traveling wave of electrical depolarization that characterizes the AP, which alter the compressive electrostatic forces across the membrane as it passes. Our model for these co-propagating mechanical displacements, which we term Action Waves (AWs) allows us to pre...

Although most of sacral perineural cysts are asymptomatic, some may produce symptoms. Specific radicular pain may be due to distortion, compression, or stretching of nerve root by a space occupying cyst. We report a rare case of S1 radiculopathy caused by sacral perineural cyst accompanying disc herniation. The patient underwent a microscopic discectomy at L5-S1 level. However, the patient's symptoms did not improved. The hypesthesia persisted, as did the right leg pain. Cyst-subarachnoid shunt was set to decompress nerve root and to equalize the cerebrospinal fluid pressure between the cephalad thecal sac and cyst. Immediately after surgery, the patient had no leg pain. After 6 months, the patient still remained free of leg pain. PMID:19352483

Background The objective of this review is to evaluate the use of electrical stimulation to treat diabetic neuropathy. Application of electrical stimulation may provide a novel treatment option for large and small fiber neuropathy in persons with diabetes. Large and small nerve neuropathy alters pain, proprioception, touch perception, and motor function, which cause burning foot pain and serve as protective mechanisms from ulcerations. Methods A content search for clinical trials involving electrical stimulation, neuropathy, and diabetes was conducted through PubMed. Randomized clinical trials and prospective studies with outcome measures affecting the lower extremity function were selected for review. Results We identified eight studies in which electrical stimulation was used to treat diabetic neuropathy. Six studies evaluated small fiber neuropathy. Two studies evaluated patients with both small and large fiber neuropathy and reported significant improvement in vibration and monofilament testing and reduction in symptoms in the electrical stimulation treatment group. Six of the eight painful neuropathy studies identified significant improvement in symptoms. There were no studies that evaluated electrical stimulation to treated diabetic motor neuropathy, fall prevention or postural instability. Conclusions Electrical stimulation may be an effective alternative and adjunctive therapy to current interventions for diabetic peripheral neuropathy. PMID:24124947

Summary A previously unrecognized neuropathy was identified in Bulgarian gypsies, and was designated hereditary motor and sensory neuropathy-Lom (HMSNL) after the town where the initial cases were found. It was subsequently identified in other gypsy communities. The disorder, which is of autosomal recessive inheritance, was mapped to chromosome 8q24. It begins consistently in the first decade of life with gait

Objective The purpose of this case report is to describe a patient who presented with a case of peroneal neuropathy that was originally diagnosed and treated as a L5 radiculopathy. Clinical features A 53-year old female registered nurse presented to a private chiropractic practice with complaints of left lateral leg pain. Three months earlier she underwent elective left L5 decompression surgery without relief of symptoms. Intervention and outcome Lumbar spine MRI seven months prior to lumbar decompression surgery revealed left neural foraminal stenosis at L5-S1. The patient symptoms resolved after she stopped crossing her legs. Conclusion This report discusses a case of undiagnosed peroneal neuropathy that underwent lumbar decompression surgery for a L5 radiculopathy. This case study demonstrates the importance of a thorough clinical examination and decision making that ensures proper patient diagnosis and management. PMID:23618508

A 7-year-old, 46-kg spayed female rottweiler dog was presented with sudden onset of disorientation, bilateral convergent strabismus, and enophthalmos. Diagnostic workup revealed hypothyroid-associated cranial neuropathy. Symptoms abated considerably upon treatment with levothyroxine-sodium (T4) at an initial dose of 800 ?g/kg body weight (BW), PO, q12h, which was reduced 3 days later to 600 ?g/kg BW, q12h due to severe agitation and panting. Two weeks later the dosage of the levothyroxine-sodium (T4) was reduced to 400 ?g/kg BW in the morning and 600 ?g/kg BW in the evening. Eight weeks after the initial presentation, the dog had recovered with only mild convergent strabismus in the right eye. This is the first case report of suspected hypothyroid-associated neuropathy resulting in these symptoms. PMID:24082164

Diabetic polyneuropathy can be easily diagnosed when the nerve conduction studies are affected. Strength Duration Time (SDTc) reflects nerve excitability properties and was previously used several times to demonstrate the excitability properties of the nerves in the existence of electrophysiologically developed diabetic polyneuropathy. But as we all know, diabetic patients may experience neuropathic symptoms even though their routine nerve conduction studies are normal. SDTc may be useful in this early stages of developing neuropathy. In this study we aimed to evaluate the SDTc properties of diabetic patients in this early preclinic stage. Recently SDTc was commonly studied in the upper extremities but most of the diabetic neuropathies are predominant in the lower extremities. So here we also studied both upper and lower extremities to demonstrate a possible difference. PMID:21741106

Clinical, electromyographic, and pathologic findings characteristic of lead toxicosis were detected in a turkey vulture (Cathartes aura). The bird had generalized lower motor neuron dysfunction that progressed over 5 days. Electromyography revealed diffuse denervation potentials and a presumed decrement in the sciatic-tibial nerve conduction velocity. Histologic examination of peripheral nerves obtained at necropsy revealed changes that could be compatible with lead-induced neuropathy. Lead toxicosis was confirmed by determination of blood lead concentrations. Lead toxicosis causing neurologic disorders in birds has been described. However, this report emphasizes the effects of lead on the peripheral nervous system and demonstrates the use of electromyography for diagnosis of peripheral neuropathy in birds. PMID:10212687

Paclitaxel is an antineoplastic agent derived from the bark of the western yew, Taxus brevifolia, with a broad spectrum of activity. Because paclitaxel promotes microtubule assembly, neurotoxicity is one of its side effects. Clinical use of paclitaxel has led to peripheral neuropathy and this has been demonstrated to be dependent upon the dose administered, the duration of the infusion, and the schedule of administration. Vehicles in the drug formulation, for example Cremophor in Taxol, have been investigated for their potential to induce peripheral neuropathy. A variety of neuroprotective agents have been tested in animal and clinical studies to prevent paclitaxel neurotoxicity. Recently, novel paclitaxel formulations have been developed to minimize toxicities. This review focuses on recent advances in the etiology of paclitaxel-mediated peripheral neurotoxicity, and discusses current and ongoing strategies for amelioration of this side effect. PMID:18615126

Peripheral neuropathies are well-known complications of primary systemic vasculitides. In rare cases, peripheral neuropathies are among the first symptoms of these diseases. In this prospective study, 89 consecutive adult patients with newly diagnosed primary systemic vasculitis were screened, of whom 22 patients (25 %, 12 men, ten women, mean age, 59 years, range, 26-82 years) suffered from peripheral neuropathy due to systemic vasculitis at initial presentation. Peripheral neuropathy was most frequent in newly diagnosed patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome, 12 out of 20 patients, 60 %) and polyarteritis nodosa (three out of six patients, 50 %), and less common in patients with granulomatosis with polyangiitis (six out of 47 patients, 13 %) and microscopic polyangiitis (one out of 16 patients, 6 %). Multiplex mononeuropathy was more frequent (n = 13, 59 %) than symmetric polyneuropathy (n = 9, 41 %). The nerves commonly affected were the peroneal nerve, followed by the sural, posterior tibial, and median nerves. Treatment options were chosen according to current guidelines of the national neurological and rheumatologic societies, with initial corticosteroid monotherapy for patients with a mild disease form and a combination of corticosteroids and intravenously pulsed cyclophosphamide for patients with a more extended organ involvement. During follow-up (mean, 34 months, range, 12-112 months), new neurological complications were rare (9 %): One patient suffered from a cerebral infarct while another patient sustained epileptic seizures. Two patients (9 %) died from sepsis (after 60 months) or severe gastrointestinal bleeding (after 13 months). The degree of neurological disability measured by the functional disability score (described by Prineas) improved in 20 of 22 patients after 12 months of therapy. PMID:23212754

The authors evaluated the usefulness of current perception threshold testing for the assessment of vibration-induced neuropathy. The study population comprised 20 male controls and 59 males with hand-arm vibration syndrome. Current perception threshold at three test frequencies (i.e., 5 Hz, 250 Hz, and 2,000 Hz) was determined on the distal phalanges of the index and little fingers. Large myelinated fibers,

We report the clinical and imaging features of a patient with transient partial trigeminal sensory neuropathy thought to have been induced by thermal injury to the tongue. Abnormal thickening and enhancement of the mandibular division of the trigeminal nerve was revealed by MR imaging. The diagnostic considerations for mass-like enlargement of the trigeminal nerve should include transient/inflammatory processes, as well as more common and sinister conditions, such as tumor. PMID:10669251

I review auditory neuropathy (AN), an auditory temporal processing disorder, drawing upon lessons from patients, from temporal\\u000a bones and peripheral nerves, and from the genetics of the disorder. The auditory temporal processing disorder affects speech\\u000a comprehension and localization of sounds that can be disabling. Audibility is typically not the majoy problem. The criteria\\u000a for diagnosis are physiological and include (1)

Multifocal motor neuropathy (MMN) is a rare inflammatory, chronically progressive, unremitting disorder affecting the peripheral nervous system. Although the etiology of this condition is not known, high titers of IgM Ab to GM1 may serve as a biomarker for this disease. Clinical findings of motor weakness are associated with focal conduction blocks and with time, axonal destruction. Evidence supporting an immune etiology as well as the use of intravenous immunoglobulin to limit the disease progression is reviewed. PMID:24699885

The common peroneal nerve (CPN), a major terminal branch of the sciatic nerve, can be subject to a variety of pathologies,\\u000a which may affect the nerve at any level from the lumbar plexus to its distal branches. Although the diagnosis of peripheral\\u000a neuropathy is traditionally based on a patient’s clinical findings and electrodiagnostic tests, magnetic resonance neurography\\u000a (MRN) is gaining

Objective Few tests of functional motor behavior are useful for rapidly screening people for lower extremity peripheral neuropathy. The goal of this study was to improve the widely used Tandem Walking test (TW). Methods We tested adult normals and ambulatory peripheral neuropathy patients (PN) with eyes open and eyes closed, while they performed TW on industrial carpeting, in sock-covered feet. Each subject wore a torso-mounted inertial motion unit to measure kinematic data. PN subjects’ data were also compared to historical data on patients with vestibular impairments (VI). Results The normal and PN groups differed significantly on TW on the number of steps completed. PN and VI data also differed significantly on both visual conditions. Kinematic data showed that PN patients were more unstable than normals. For the number of steps taken during the eyes open condition receiver operating characteristic (ROC) values were only 0.81. For the number of steps taken during the eyes closed condition, however, ROC=0.88. Although not optimal, this ROC value is better. Sensitivity and specificity at a cut-off of 2 steps were 0.81 and 0.92, respectively, and at a cut-off of 3 steps was 0.86 and 0.75, respectively. ROC values for kinematic data were all < 0.8 and, when combined with the ROC value for the number of steps, the total ROC value did not improve appreciably. Conclusions Although not ideal for screening patients who may have peripheral neuropathy, counting the number of steps during TW is a quick and useful clinical test. TW is most sensitive to peripheral neuropathy patients when they are tested with eyes closed. PMID:24096950

Objective Accumulation of mitochondrial DNA (mtDNA) damage has been associated with aging and abnormal oxidative metabolism. We hypothesized that in human immunodeficiency virus associated sensory neuropathy (HIV-SN), damaged mtDNA accumulates in distal nerve segments and that a spatial pattern of mitochondrial dysfunction contribute to the distal degeneration of sensory nerve fibers. Methods We measured levels of common deletion mutations in mtDNA and expression levels of mitochondrial respiratory chain complexes of matched proximal and distal nerve specimens from patients with and without HIV-SN. In mitochondria isolated from peripheral nerves of simian immunodeficiency virus (SIV) infected macaques, a model of HIV-SN, we measured mitochondrial function and generation of reactive oxygen species. Results We identified increased levels of mtDNA common deletion mutation in post-mortem sural nerves of patients with HIV-SN as compared to uninfected patients or HIV patients without sensory neuropathy. Furthermore, we found that common deletion mutation in mtDNA was more prevalent in distal sural nerves compared to dorsal root ganglia. In a primate model of HIV-SN, freshly isolated mitochondria from sural nerves of macaques infected with a neurovirulent strain of SIV showed impaired mitochondrial function compared to mitochondria from proximal nerve segments. Interpretation Our findings suggest that mtDNA damage accumulates in distal mitochondria of long axons, especially in patients with HIV-SN, and that this may lead to reduced mitochondrial function in distal nerves relative to proximal segments. Although our findings are based on HIV-SN, if confirmed in other neuropathies, these observations could explain the length-dependent nature of most axonal peripheral neuropathies. PMID:21280080

Objectives: Evidences of oxidative and/or nitrosative stress in type 2 diabetes mellitus were demonstrated in experimental and human studies. This study is aimed to assess the serum peroxynitrite and oxidized lipoproteins in patients with type 2 diabetes mellitus presented with clinical and laboratory evidences of peripheral neuropathy. Materials and Methods: Eighty four patients with type 2 diabetes mellitus (51 of them had neuropathy) and 31 apparent healthy subjects were studied in the unit of neurophysiology at the University Hospital of Medical College, Al-Nahrin University in Baghdad, Iraq. Neuropathy total symptom score (NTSS), neuropathy impairment score in the lower leg (NIS-LL), and nerve conduction velocity of sensory (ulnar and sural) and motor (ulnar and common peroneal) nerves were used to assess the neuropathy. Fasting venous blood was obtained from each participant for the determination of serum glucose and oxidized lipoproteins. Results: The electrophysiology study revealed significant decrease in conduction velocity of ulnar (sensory and motor components), sural, and common peroneal nerves in diabetic neuropathy compared to diabetics without neuropathy and healthy subjects. Significant high level of serum peroxynitrite was found in diabetic patients with or without neuropathy compared with non-diabetics. The changes in serum-oxidized lipoproteins in patients with diabetics with or without neuropathy were non-significantly differed from healthy subjects. Neither nitrosative stress nor oxidative stress indices correlated with the variables that are related to the neuropathy. Conclusion: It concludes that evidence of nitrosative and to less extent the oxidative stress is associated with neuropathy in type 2 diabetes mellitus and their indices not correlated with variables related to neuropathy. PMID:22346190

Optical coherence tomography (OCT) of the macula in patients with primary opticneuropathy has revealed the presence of structural changes in the neurosensory retina in addition to the nerve fibre layer. Subretinal fluid has been documented in papilloedema and non-arteritic ischaemic opticneuropathy, and may account for decreased visual acuity in affected patients. Subretinal fluid has also been described from other causes of optic nerve head swelling including diabetic papillopathy and papillitis. Drugs used in the treatment of multiple sclerosis, such as corticosteroids and fingolimod can cause decreased vision due to central serous and cystoid macular oedema sometimes confused with recurrent optic neuritis. A subset of patients with various types of optic atrophy show microcystic changes in the inner nuclear layer on spectral domain OCT imaging. The pathophysiology and visual significance of these retinal changes remain unclear, but may affect the diagnosis and management of optic nerve disorders. PMID:24627251

Nerve conduction velocity and the amplitude of nerve and muscle action potentials have been measured in the median and anterior tibial nerves of normal adult and infant baboons. The effect of altered temperature on velocity has also been investigated. Seven adult baboons were intoxicated with acrylamide. In animals given 10-15 mg/kg/day, the gradual development of a peripheral neuropathy was accompanied by a decline in the amplitude of both muscle and nerve action potentials. There was also a gradual fall in conduction velocity. In some cases maximal motor velocity in the median nerve fell by as much as 34%, and in the anterior tibial nerve by as much as 49%, the largest falls being seen in animals showing the greatest reductions in response amplitude. Histological studies, reported elsewhere, have shown that the main pathological change in our animals was a degeneration of the peripheral nerves, with little demyelination. Fibre diameter histograms indicated that large fibres were particularly severely affected, and it seems likely that the reduced maximal conduction velocities were due to this selective loss of large-diameter fibres. PMID:4328885

We used immunohistochemistry to examine myosin heavy-chain (MyHC)-based fiber-type profiles of the right and left cricoarytenoideus dorsalis (CAD) and arytenoideus transversus (TrA) muscles of six horses without laryngoscopic evidence of recurrent laryngeal neuropathy (RLN). Results showed that CAD and TrA muscles have the same slow, 2a, and 2x fibers as equine limb muscles, but not the faster contracting fibers expressing extraocular and 2B MyHCs found in laryngeal muscles of small mammals. Muscles from three horses showed fiber-type grouping bilaterally in the TrA muscles, but only in the left CAD. Fiber-type grouping suggests that denervation and reinnervation of fibers had occurred, and that these horses had subclinical RLN. There was a virtual elimination of 2x fibers in these muscles, accompanied by a significant increase in the percentage of 2a and slow fibers, and hypertrophy of these fiber types. The results suggest that multiple pathophysiological mechanisms are at work in early RLN, including selective denervation and reinnervation of 2x muscle fibers, corruption of neural impulse traffic that regulates 2x and slow muscle fiber types, and compensatory hypertrophy of remaining fibers. We conclude that horses afflicted with mild RLN are able to remain subclinical by compensatory hypertrophy of surviving muscle fibers. PMID:19398607

We used immunohistochemistry to examine myosin heavy-chain (MyHC)-based fiber-type profiles of the right and left cricoarytenoideus dorsalis (CAD) and arytenoideus transversus (TrA) muscles of six horses without laryngoscopic evidence of recurrent laryngeal neuropathy (RLN). Results showed that CAD and TrA muscles have the same slow, 2a, and 2x fibers as equine limb muscles, but not the faster contracting fibers expressing extraocular and 2B MyHCs found in laryngeal muscles of small mammals. Muscles from three horses showed fiber-type grouping bilaterally in the TrA muscles, but only in the left CAD. Fiber-type grouping suggests that denervation and reinnervation of fibers had occurred, and that these horses had subclinical RLN. There was a virtual elimination of 2x fibers in these muscles, accompanied by a significant increase in the percentage of 2a and slow fibers, and hypertrophy of these fiber types. The results suggest that multiple pathophysiological mechanisms are at work in early RLN, including selective denervation and reinnervation of 2x muscle fibers, corruption of neural impulse traffic that regulates 2x and slow muscle fiber types, and compensatory hypertrophy of remaining fibers. We conclude that horses afflicted with mild RLN are able to remain subclinical by compensatory hypertrophy of surviving muscle fibers. (J Histochem Cytochem 57:787–800, 2009) PMID:19398607

Leprosy (also known as Hansen's Disease) is a chronic infectious disease caused by Mycobacterium leprae that primarily targets the peripheral nervous system; skin, muscle, and other tissues are also affected. Other than humans, nine-banded armadillos (Dasypus novemcinctus) are the only natural hosts of M. leprae, and they are the only laboratory animals that develop extensive neurological involvement with this bacterium. Infection in the armadillo closely recapitulates many of the structural, physiological, and functional aspects of leprosy seen in humans. Armadillos can be useful models of leprosy for basic scientific investigations into the pathogenesis of leprosy neuropathy and its associated myopathies, as well as for translational research studies in piloting new diagnostic methods or therapeutic interventions. Practical and ethical constraints often limit investigation into human neuropathies, but armadillos are an abundant source of leprotic neurologic fibers. Studies with these animals may provide new insights into the mechanisms involved in leprosy that also might benefit the understanding of other demyelinating neuropathies. Although there is only a limited supply of armadillo-specific reagents, the armadillo whole genomic sequence has been completed, and gene expression studies can be employed. Clinical procedures, such as electrophysiological nerve conduction testing, provide a functional assessment of armadillo nerves. A variety of standard histopathological and immunopathological procedures including Epidermal Nerve Fiber Density (ENFD) analysis, Schwann Cell Density, and analysis for other conserved cellular markers can be used effectively with armadillos and will be briefly reviewed in this text. PMID:24615444

High dose pyridoxine is neurotoxic. Previous case reports were sparse and little is known about the clinical and electrodiagnostic findings. Three patients with pyridoxine-induced sensory ataxic neuropathy were studied and a review of the involved literature was performed. Three patients, aged 80, 83 and 83 years old, presented with sensory ataxia for 3-8 months. Examination showed signs of polyneuropathy and sensory ataxia. Six hundred milligrams of pyridoxine was consumed each day for 3-10 years, in the form of vitamin B1-6-12 combination tablet. Investigations for other causes of neuropathy were unremarkable. Blood levels of vitamin B6 were markedly elevated at 104.6, 81.4 and 66.9 times of upper normal limits. Electrodiagnostic tests showed symmetric axonal sensory polyneuropathy in two patients. Two years after vitamin discontinuation, all patients showed no significant improvement in the neuropathy and gait. In conclusion, consumption of high dose pyridoxine can cause sensory neuronopathy and axonal sensorimotor polyneuropathy, leading to sensory ataxia which may not be reversible. PMID:25056196

A strain of rapidly growing meat-type chickens was fed a diet deficient in riboflavin from 1-40 days of age. Diminished growth rate, progressive gait abnormality and reluctance to move were noted beginning on day 8. Neurologic abnormalities were related to peripheral neuropathy characterized by Schwann cell hypertrophy and degeneration with cytoplasmic lipid droplets' and segmental demyelination. Lesions were initially detected on day 10, and in concert with clinical signs became more profound between days 14 and 21. Sequestration of myelin debris within Schwann cells was common. Other features of the neuropathy included the presence of endoneurial edema and axonal degeneration involving small numbers of fibers. Remyelination of peripheral nerve fibers in birds on the deficient diet was occasionally seen on day 10, became progressively more prominent, and was marked by day 37. There was an associated, variable but incomplete, clinical improvement evident in later stages of the study. Liver concentrations of riboflavin in deficient birds were significantly reduced on day 13 but not on day 26. This neuropathy may be related to diminished tissue levels of the riboflavin-based coenzymes flavin-adenine dinucleotide (FAD) and flavin mononucleotide (FMN) leading to reduced cellular energy levels and profoundly affecting Schwann cells at some critical point in growth. PMID:3040915

Neuropathies of the peripheral and autonomic nervous systems affect up to half of all people with diabetes, and are major risk factors for foot ulceration and amputation. The aetiology is multifactorial: metabolic changes in diabetes may directly affect neural tissue, but importantly, neurodegenerative changes are precipitated by compromised nerve vascular supply. Experiments in animal models of diabetic neuropathy suggest that similar metabolic sequelae affect neurons and vasa nervorum endothelium. These include elevated polyol pathway activity, oxidative stress, the formation of advanced glycation and lipoxidation end products, and various pro-inflammatory changes such as elevated protein kinase C, nuclear factor ?B and p38 mitogen activated protein kinase signalling. These mechanisms do not work in isolation but strongly interact in a mutually facilitatory fashion. Nitrosative stress and the induction of the enzyme poly (ADP-ribose) polymerase form one important link between physiological stressors such as reactive oxygen species and the pro-inflammatory mechanisms. Recently, evidence points to endoplasmic stress and the unfolded protein response as forming another crucial link. This review focuses on the aetiopathogenesis of neurovascular changes in diabetic neuropathy, elucidated in animal studies, and on putative therapeutic targets the majority of which have yet to be tested for efficacy in clinical trials. PMID:23872412

Back ground: Vincristine (VCR), is a chemotherapy drug, useful in the treatment of leukemia, lymphoma and solid tumor and it is a potent neurotoxin and sensory neuropathy drug which a common behavioral toxicity of this drug. Neuropathy is common squeal of intensive chemotherapy protocols that contain vincristine and corticosteroids. Materials and Methods: This study was a retrospective and descriptive study of neuropathy during in chemotherapy program with vincristine for patients with non-Hodgkin's lymphoma (NHL) and Acute Lymphoblastic Leukemia (ALL). Data was analyzed by spss Version16 software. Results: From total of 51 cases, 23 patients had vincristine neuropathy (45%). Patients with visceral neuropathy have shown ileus, constipation in 13 patients (25%), occasionally severe diarrhea 11 (21%), mild diarrhea 7 (13.7%) and transient diarrhea in 16 patients (31%). Motor neuropathy were found in one patient with Bell, s palsy (1.9%) and one patient with Hoarseness. 12 patients (23.5%) had some type of complication together with sensory peripheral neuropathy. Conclusion: Almost half of patients with vincristin chemotherapy had neuropathy and the mean age of patients with neuropathy was 12.3 years. PMID:24575286

??Diabetes is an increasingly prevalent disease worldwide. Providing early management of the complications can prevent morbidity and mortality in this population. Peripheral neuropathy, a significant… (more)

This page allows users to simulate standard optic elements (lens, mirror, dielectrics, sources, apertures) and observe how light rays propagate through these elements. Element properties, such as position and focal length, can be adjusted using and a click and drag metaphor.

Inherited disorders of peripheral nerves represent a common group of neurologic diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is a genetically heterogeneous group of chronic demyelinating polyneuropathies with loci mapping to chromosome 17 (CMT1A), chromosome 1 (CMT1B), chromosome 16 (CMT1C) and chromosome 10 (CMT1D). CMT1A is most often associated with a tandem 1.5-megabase (Mb) duplication in chromosome 17p11.2-p12. In rare patients it may result from a point mutation in the peripheral myelin protein-22 (PMP22) gene. CMT1B is associated with point mutations in the myelin protein zero (Po or MPZ) gene. Mutations in the SIMPLE gene cause CMT1C, and CMT1D is the result of mutations in the early response 2 (ERG2 or Krox-20) gene. An X-linked form of CMT1 (CMT1X) maps to Xq13 and is associated with mutations in the connexin32 (Cx32) gene. Charcot-Marie-Tooth neuropathy type 2 (CMT2) is an axonal neuropathy that maps to chromosome 1p35-p36 (CMT2A), chromosome 3q13-q22 (CMT2B), chromosome 7p14 (CMT2D), chromosome 8p21 (CMT2E), chromosome 1q22-q23 (CMT2F) or chromosome 3q13 (CMT2G). Two X-linked forms of CMT2 have been reported (CMT2XA and CMT2XB), but the genes remain unidentified. An area that has recently expanded is the identification of autosomal recessive forms of CMT type 1 and 2. Of the eight recessive forms of CMT1 that have been identified to date, only two have been fully characterized at the molecular level (CMT1 AR B 1 and CMT1 AR D). Point mutations were found in the myotubularin-related protein-2 (MTM2) gene for CMT1 AR B1. CMT1 AR D is the result of point mutations in the N-myc downstream-regulated gene 1 (NDRG1). Dejerine-Sottas disease (DSD), also called hereditary motor and sensory neuropathy type III (HMSNIII), is a severe, infantile-onset demyelinating polyneuropathy syndrome that may be associated with point mutations in either the PMP22 gene, PO gene, EGR2 gene or the PRX gene (for the recessive form). It shares considerable clinical and pathological features with CMT1. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that results in a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-p12 that results in reduced expression of the PMP22 gene. CMT1A and HNPP are reciprocal duplication/deletion syndromes that originate from unequal crossover during germ cell meiosis. Other rare forms of demyelinating peripheral neuropathies map to chromosome 8q, 10q and 11q. PMID:16106622

??Peripheral neuropathy is a well-documented complication of diabetes, yet it remains an underappreciated condition in non-diabetic individuals. Studies of neuropathy in longitudinal or population-based samples… (more)

...VA's proposed rule, stating that he is not a veteran and that he was diagnosed with peripheral neuropathy as the result of shingles. VA recognizes that peripheral neuropathy is not unique to veterans or exposure to Agent Orange. However, as explained...

Summary A double blind crossover study with placebo and carbamazepine was done in 30 diabetic patients who presented diverse clinical types of peripheral diabetic neuropathy. The active drug offered symptomatic relief of all sensory manifestations in 28 cases. No effort was made to assess the action of carbamazepine upon motor or visceral manifestations of neuropathy. There were two complete failures. Untoward

A prospective study in South-East England during 15 months in 1983-1984 recruited 100 patients with acute idiopathic neuropathy. After 12 months 67% had recovered completely, 20% were still significantly disabled and 13% had died. Ten of the 13 deaths were attributable to the neuropathy. The major features in the initial assessment which were associated with persistent disability were the time

The sympathetic skin response (SSR) was measured in 33 patients with peripheral neuropathies and in 30 normal control subjects. Abnormalities of the response were correlated with clinical, pathologic, and EMG observations. The response was usually absent in axonal neuropathies, but present in demyelinating disorders. Abnormalities of the sympathetic skin response did not correlate well with clinical evidence of dysautonomia, but

Summary QT intervals were measured over RR intervals ranging from 500 ms to 1000 ms in 13 normal male subjects, 13 male diabetic subjects without and 13 with autonomic neuropathy. There was a close linear relationship between QT and RR in all subjects. The slope of the regression line was significantly greater in the autonomic neuropathy group than the normal group.

Plasma exchange was used to treat 10 patients with polyneuropathy and a monoclonal antibody (plasma cell dyscrasia). Six patients had improvement of the neuropathy, while three patients had stabilisation of the neuropathy during plasma exchange. The patients who improved maintained a 64% or greater decrease in the monoclonal antibody between exchanges. Patients with axonal polyneuropathy as well as patients with

Diabetes is said to account for most cases of neuropathy in the elderly. We reviewed records of 223 young-old (65-79 years) and 77 old-old (>or=80 years) patients referred for evaluation of neuropathic symptoms over a 9-year period. We prospectively validated our findings in 102 consecutive elderly (77 young-old) patients receiving intensive evaluation for neuropathy. Diabetes was the most common cause of neuropathy (41%), but was less common in the old-old (25% versus 46%, P < 0.001). Idiopathic neuropathies were more common in the old-old (39% versus 9%, P < 0.001). Alcoholic and nutritional neuropathies were uncommon in the old-old. Electrophysiological studies showed that most patients had an axonal type of neuropathy. Sural and peroneal response amplitudes were poorly correlated with age. We obtained similar results in our prospective study. The distribution of causes of neuropathies in young-old and old-old patients, in a hospital-based sample, is age-related. Future studies need to include the old-old to better understand the nature of neuropathy in the elderly. PMID:11745949

Chronic alcohol consumption produces a painful peripheral neuropathy for which there is no reliable successful therapy, which is mainly due to lack of understanding of its pathobiology. Alcoholic neuropathy is characterized by spontaneous burning pain, hyperalgesia (an exaggerated pain in response to painful stimuli) and allodynia (a pain evoked by normally innocuous stimuli). Chronic alcohol intake is known to decrease

Immune mediated neuropathies are uncommon but important to diagnose because they are potentially treatable. This chapter summarizes the clinical approach to diagnosis of Guillain Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and related neuropathies which are thought to be caused by direct autoimmune attack on peripheral nerves. PMID:24434363

We describe the occurrence of small fiber neuropathy in a patient affected by Chagas disease in the indeterminate phase. After the exclusion of all the possible etiologies of small fiber neuropathy, the disorder was considered related to Trypanosoma cruzi infection. Although a peripheral involvement has been described in Chagas disease, this is the first report of a selective involvement of small fibers. PMID:23475268

1/13 Clinical Features: Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus sensorimotor neuropathy resulting in hypotonia, areflexia and amyotrophy, variable degrees of dysgenesis Neuropathy with Agenesis of the Corpus Callosum #12;1/13 Prenatal testing for a known mutation Sample

PURPOSE. Glaucomatous opticneuropathy is characterized by remodeling of the extracellular matrix with disorganization of elastic fibers in the optic nerve head (ONH). There are signif- icant differences in prevalence of glaucomatous optic neurop- athy between African Americans (AAs) and Caucasian Ameri- cans (CAs). The goal of this study was to evaluate differences in elastin synthesis and maturation in ONH

Many listeners with hearing thresholds within the clinically normal range nonetheless complain of difficulty hearing in everyday settings and understanding speech in noise. Converging evidence from human and animal studies points to one potential source of such difficulties: differences in the fidelity with which supra-threshold sound is encoded in the early portions of the auditory pathway. Measures of auditory subcortical steady-state responses (SSSRs) in humans and animals support the idea that the temporal precision of the early auditory representation can be poor even when hearing thresholds are normal. In humans with normal hearing thresholds (NHTs), paradigms that require listeners to make use of the detailed spectro-temporal structure of supra-threshold sound, such as selective attention and discrimination of frequency modulation (FM), reveal individual differences that correlate with subcortical temporal coding precision. Animal studies show that noise exposure and aging can cause a loss of a large percentage of auditory nerve fibers (ANFs) without any significant change in measured audiograms. Here, we argue that cochlear neuropathy may reduce encoding precision of supra-threshold sound, and that this manifests both behaviorally and in SSSRs in humans. Furthermore, recent studies suggest that noise-induced neuropathy may be selective for higher-threshold, lower-spontaneous-rate nerve fibers. Based on our hypothesis, we suggest some approaches that may yield particularly sensitive, objective measures of supra-threshold coding deficits that arise due to neuropathy. Finally, we comment on the potential clinical significance of these ideas and identify areas for future investigation. PMID:24600357

Giant axonal neuropathy is a rare autosomal recessive childhood disorder characterized by a peripheral neuropathy and features of central nervous system involvement. Magnetic resonance imaging (MRI) of an 11-year-old boy with giant axonal neuropathy revealed high signal intensity in the white matter of the cerebrum and cerebellum on T(2)-weighted imaging. An apparent diffusion coefficient map revealed increased apparent diffusion coefficient values in the periventricular, deep, and cerebellar white matter, basal ganglia, and thalamus. Increased apparent diffusion coefficient values in distinct locations suggest increased mobility of water molecules in the brain of a patient with giant axonal neuropathy. This finding could indicate a myelin disorder such as demyelination. Diffusion-weighted imaging should be performed to reveal apparent diffusion coefficient changes and determine brain involvement in patients with giant axonal neuropathy. PMID:17005115

Mutations in myelin protein zero (MPZ) protein result in a wide spectrum of peripheral neuropathies, from congenital hypomyelinating to late onset sensory and motor axonal forms. In some patients, neuropathic pain can be a prominent symptom, making the diagnosis challenging mainly in those with other risk factors for neuropathy. We describe a 77-year-old woman with impaired glucose tolerance presenting with rapidly progressive axonal neuropathy leading to excruciating pain and severe weakness of lower limbs within 2?years from the onset. Her son abruptly complained of similar painful symptoms at the age of 47 years. Molecular analysis revealed a novel heterozygous missense mutation (c.106A>G) in MPZ exon 2, causing the substitution of arginine-36 with glycine in the extracellular domain. Our observation suggests that MPZ-related neuropathy should be considered in the diagnostic work up of patients with painful axonal neuropathy even presenting with rapid progression and at a very late age of onset. PMID:23279346

The role and relevance of deamidated gliadin antibodies specific for celiac disease in gluten-sensitive ataxia/ neuropathy is unknown. We investigated the association of celiac-specific serology with gluten-sensitive ataxia/neuropathy, in patients with and without gliadin-induced enteropathy. 51 patients with unexplained ataxia/neuropathy suspected to have gluten sensitivity were included in the study and their serum celiac specific markers were measured. Deamidated-gliadin-IgA (83% vs 22%), deamidated-gliadin-IgG (50% vs 3%), tissue-transglutaminase-IgA (78% vs 11%), and anti-endomysial-IgA (70% vs 0%), were significantly more positive in ataxia/neuropathy patients with celiac disease versus those without enteropathy (P <0.001). Our findings suggest that the serological profile of gluten-sensitive ataxia/neuropathy without intestinal involvement lacks the recognition of deamidated-gliadin and tissue-transglutaminase epitopes. PMID:21056914

Painful peripheral neuropathy often occurs without apparent underlying cause. Gain-of-function variants of sodium channel Nav1.7 have recently been found in ?30% of cases of idiopathic painful small-fiber neuropathy. Here, we describe mutations in Nav1.8, another sodium channel that is specifically expressed in dorsal root ganglion (DRG) neurons and peripheral nerve axons, in patients with painful neuropathy. Seven Nav1.8 mutations were identified in 9 subjects within a series of 104 patients with painful predominantly small-fiber neuropathy. Three mutations met criteria for potential pathogenicity based on predictive algorithms and were assessed by voltage and current clamp. Functional profiling showed that two of these three Nav1.8 mutations enhance the channel’s response to depolarization and produce hyperexcitability in DRG neurons. These observations suggest that mutations of Nav1.8 contribute to painful peripheral neuropathy. PMID:23115331

Sensory peripheral neuropathy developed in 5 patients treated with almitrine dimesylate, 60-100 mg/day. Onset was insidious, beginning symmetrically in the legs with stocking sensory loss and loss of ankle-jerks. Cerebrospinal fluid protein levels were slightly increased and there was electrophysiological and histological evidence of distal axonopathy. The interval between the first dose of almitrine dimesylate and onset of symptoms ranged from 2 to 4 months in 4 patients. All patients had noted a recent weight loss of 4-15 kg which may have resulted in release of previously bound drug. PMID:2860446

Almitrine bismesylate is thought to cause sensory peripheral neuropathy. Forty-six patients are reported who received almitrine bismesylate alone for chronic respiratory failure or in combination with raubasine for various cerebrovascular diseases. Polyneuropathy appeared between 9 and 25 months after the onset of treatment. Sensory signs and symptoms were confined to the distal parts of the lower limbs and involved large and small fibres. Histological and electrophysiological findings indicated axonal degeneration. Respiratory failure could have caused the polyneuropathy in some cases but many had no chest disease. Patients began to improve between 3 and 6 months after withdrawal of the drug. Recovery was usually complete after 12 months. PMID:2536801

Chemotherapy-induced peripheral neuropathies (CIPNs) are an increasingly common neuropathic and pain syndrome in adult and pediatric cancer patients and survivors [1–69]. However, symptoms associated with CIPNs are often undiagnosed, under-assessed, and communications problems between clinicians, family members, and patients have been observed [70–73]. Less is known about the prevalence and impact of CIPNs on pediatric cancer populations [70–71]. This article aims to provide a brief understanding of CIPNs in pediatric populations, and to review the evidence for both its prevention and treatment. PMID:25144779

Hereditary sensory autonomic neuropathy type IV (HSAN -IV), also known as congenital insensitivity to pain with anhidrosis, is a very rare condition that presents in infancy with anhidrosis, absence of pain sensation and self -mutilation. Developmental delay and mental retardation are usually present. Ultrastructural study of the peripheral nerves demonstrates loss of the unmyelinated and small myelinated fibers. We here report a 8 year -old boy with HSAN IV with typical clinical features where the diagnosis was supported by nerve biopsy findings. However, our case was unusual since mental development was normal. PMID:22566729

Hereditary sensory autonomic neuropathy type IV (HSAN -IV), also known as congenital insensitivity to pain with anhidrosis, is a very rare condition that presents in infancy with anhidrosis, absence of pain sensation and self -mutilation. Developmental delay and mental retardation are usually present. Ultrastructural study of the peripheral nerves demonstrates loss of the unmyelinated and small myelinated fibers. We here report a 8 year -old boy with HSAN IV with typical clinical features where the diagnosis was supported by nerve biopsy findings. However, our case was unusual since mental development was normal. PMID:22566729

Background Chronic neuropathy after hernia repair is a neglected problem as very few patients are referred for surgical treatment. The\\u000a aim of the present study was to assess the outcome of standardized surgical revision for neuropathic pain after hernia repair.\\u000a \\u000a \\u000a \\u000a Methods In a prospective cohort study we evaluated all patients admitted to our tertiary referral center for surgical treatment of\\u000a persistent neuropathic

The Department of Veterans Affairs (VA) adopts as a final rule its proposal to amend its adjudication regulations by clarifying and expanding the terminology regarding presumptive service connection for acute and subacute peripheral neuropathy associated with exposure to certain herbicide agents. This amendment implements a decision by the Secretary of Veterans Affairs based on findings from the National Academy of Sciences (NAS) Institute of Medicine report, Veterans and Agent Orange: Update 2010. It also amends VA's regulation governing retroactive awards for certain diseases associated with herbicide exposure as required by court orders in the class action litigation of Nehmer v. U.S. Department of Veterans Affairs. PMID:24040683

Objective: to determine the prevalence of restless legs syndrome (RLS) in a cohort of patients with demyelinating neuropathies. Methods: Patients were retrospectively recruited from our cohort of different forms of demyelinating neuropathies, including chronic inflammatory demyelinating neuropathy (CIDP), Charcot-Marie-Tooth 1A (CMT1A), and hereditary neuropathy with liability to pressure palsies (HNPP) referred to our Department of Neurology in a 10-year period. The validated 4-item RLS questionnaire was used for diagnosis of RLS. All patients with RLS who fulfilled criteria underwent a suggested immobilization test to confirm the diagnosis. A group of outpatients referred to the sleep disorders unit and data from published literature were used as controls. Results: Prevalence of RLS in demyelinating neuropathy group was higher than prevalence observed in control population (p = 0.0142) or in the literature data (p = 0.0007). In particular, in comparison with both control population and literature data, prevalence of RLS was higher in CIDP group (p = 0.0266 and p = 0.0063, respectively) and in CMT1A group (p = 0.0312 and p = 0.0105, respectively), but not in HNPP (p = 1.000 and p = 0.9320, respectively). Conclusions: our study confirms a high prevalence of RLS in inflammatory neuropathies as CIDP and, among inherited neuropathies, in CMT1A but not in HNPP. Considering that this is only a small cohort from a single-center retrospective experience, the link between RLS and neuropathy remains uncertain, and larger multicenter studies are probably needed to clarify the real meaning of the association between RLS and neuropathy. Citation: Luigetti M; Del Grande A; Testani E; Bisogni G; Losurdo A; Giannantoni NM; Mazza S; Sabatelli M; Della Marca G. Restless leg syndrome in different types of demyelinating neuropathies: a single-center pilot study. J Clin Sleep Med 2013;9(9):945-949. PMID:23997707

Objective To study retinal morphological changes around the optic disc in patients with peripapillary atrophy (PPA) with high-resolution spectral domain optical coherence tomography (SD OCT). Design Cross-sectional, retrospective analysis Participants One hundred and three eyes of 73 patients with PPA and 21 eyes of 12 normal patients seen at the New England Eye Center, Tufts Medical Center between January 2007 and August 2009. Methods SD OCT images taken through the region of PPA were quantitatively and qualitatively analyzed. Inclusion criteria included eyes with at least 300 ?m of temporal PPA as detected on color fundus photographs. The study population was divided into subgroups according to the following clinical diagnoses: glaucoma (n=13), age-related macular degeneration (n=11), high myopia (n=11), glaucoma and high myopia (n=3), and opticneuropathy (n=11). Fifty-four patients were classified with other diagnoses. Using OCT software, retinal thickness and retinal nerve fiber layer thickness (RNFL) were both manually measured perpendicular to the internal limiting membrane and retinal pigment epithelium (RPE) 300 ?m temporal to the optic disc, within the region of peripapillary atrophy. Qualitative analysis for morphological changes in the atrophic area was also performed. Main outcome measures Qualitative assessment and quantitative measures of retinal and retinal nerve fiber layer thickness in PPA. Results The study group was categorized by 6 characteristics demonstrated in the area of PPA by SD OCT: RPE loss with accompanying photoreceptor loss, RPE disruption, RNFL thickening with plaque-like formation, intraretinal cystic changes, inner and outer retinal thinning, and abnormal retinal sloping. Statistical analysis of measurements revealed a statistically significant difference in the total retinal thickness between normal eyes and eyes with PPA (p = 0.0005), with normals 15% thicker than the PPA group; however, the RNFL thickness was not significantly different between the normal and PPA group (p = 0.05). Conclusion Eyes with peripapillary atrophy manifest characteristic retinal changes that can be described via SD OCT. PMID:20920826

Separating singing voice from music accompaniment is very useful in many applications, such as lyrics recognition and alignment, singer identification, and music information retrieval. Although speech separation has been extensively studied for decades, singing voice separation has been little investigated. We propose a system to separate singing voice from music accompaniment for monaural recordings. Our system consists of three stages.

Neuropathy target esterase (NTE) is a membrane protein found in human neurons and other cells, including lymphocytes. Binding of certain organophosphorus (OP) compounds to NTE is believed to cause OP-induced delayed neuropathy (OPIDN), a type of paralysis for which there is no effective treatment. Mutations in NTE have also been linked with serious neurological diseases, such as motor neuron disease. This paper describes development of the first nanostructured biosensor interface containing a catalytically active fragment of NTE known as NEST. The biosensor was fabricated using the layer-by-layer assembly approach, by immobilizing a layer of NEST on top of multilayers consisting of a polyelectrolyte (poly-L-lysine) and an enzyme (tyrosinase). The biosensor has a response time on the order of seconds and gives a concentration-dependent decrease in sensor output in response to a known NEST (and NTE) inhibitor. Potential applications of the biosensor include screening OP compounds for NTE inhibition and investigating the enzymology of wild-type and mutant forms of NTE. Although the development of a NEST biosensor was the primary purpose of this study, we found that the approach developed for NEST could also be extended to measure the activity of other esterases involved in neural processes, such as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). On the basis of measured sensitivities, phenyl valerate was the preferred substrate for NEST and BChE, whereas phenyl acetate was better for AChE. PMID:17555296

Cardiac autonomic neuropathy (CAN) is an often overlooked and common complication of diabetes mellitus. CAN is associated with increased cardiovascular morbidity and mortality. The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death. In addition, autoimmune and genetic factors are involved in the development of CAN. CAN might be subclinical for several years until the patient develops resting tachycardia, exercise intolerance, postural hypotension, cardiac dysfunction and diabetic cardiomyopathy. During its sub-clinical phase, heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic. Newer imaging techniques (such as scintigraphy) have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system. One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN; however, the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN, and also proposed screening for CAN in patients with diabetes mellitus. A major challenge, however, is the lack of specific treatment to slow the progression or prevent the development of CAN. Lifestyle changes, improved metabolic control might prevent or slow the progression of CAN. Reversal will require combination of these treatments with new targeted therapeutic approaches. The aim of this article is to review the latest evidence regarding the epidemiology, pathogenesis, manifestations, diagnosis and treatment for CAN. PMID:24567799

Multifocal motor neuropathy (MMN) is an uncommon, purely motor neuropathy associated with asymmetric deficits with predilection for upper limb involvement. Even in the early descriptions of MMN, the associations of anti-GM1 antibodies and robust response to immunomodulatory treatment were recognized. These features highlight the likelihood of an underlying autoimmune etiology of MMN. The clinical presentation of MMN can closely mimic several neurological conditions including those with more malignant prognoses such as motor neuron disease. Therefore early and rapid recognition of MMN is critical. Serological evidence of anti GM-1 antibodies and electrodiagnostic findings of conduction block are helpful diagnostic clues for MMN. Importantly, these diagnostic features are not universally present, and patients lacking these characteristic findings can demonstrate similar robust response to immunodulatory treatment. In the current review, recent research in the areas of diagnosis, pathogenesis, and treatment of MMN and needs for the future are discussed. The characteristic findings of MMN and treatment implications are reviewed and contrasted with other mimicking disorders. PMID:24741315

The neuromuscular junction (NMJ) is a specialized synapse with a complex molecular architecture that provides for reliable transmission between the nerve terminal and muscle fiber. Using linkage analysis and whole-exome sequencing of DNA samples from subjects with distal hereditary motor neuropathy type VII, we identified a mutation in SLC5A7, which encodes the presynaptic choline transporter (CHT), a critical determinant of synaptic acetylcholine synthesis and release at the NMJ. This dominantly segregating SLC5A7 mutation truncates the encoded product just beyond the final transmembrane domain, eliminating cytosolic-C-terminus sequences known to regulate surface transporter trafficking. Choline-transport assays in both transfected cells and monocytes from affected individuals revealed significant reductions in hemicholinium-3-sensitive choline uptake, a finding consistent with a dominant-negative mode of action. The discovery of CHT dysfunction underlying motor neuropathy identifies a biological basis for this group of conditions and widens the spectrum of disorders that derive from impaired NMJ transmission. Our findings compel consideration of mutations in SLC5A7 or its functional partners in relation to unexplained motor neuronopathies. PMID:23141292

Diabetic peripheral neuropathy (DPN) is a frequent complication of diabetes and a major cause of morbidity and increased mortality. It is typically characterized by significant deficits in tactile sensitivity, vibration sense, lower-limb proprioception, and kinesthesia. Painful diabetic neuropathy (P-DPN) is a common phenotype of DPN that affects up to one-third of the general diabetic population. P-DPN has been shown to be associated with significant reductions in overall quality of life, increased levels of anxiety and depression, sleep impairment, and greater gait variability. The purpose of this review is to examine proposed mechanisms of P-DPN, summarize current treatment regimen, and assess exercise as a potential therapy for P-PDN. Although exercise has been shown to be an effective therapeutic modality for diabetes, its specific effects on DPN and especially the painful phenotype have not been sufficiently investigated in current literature. Several rodent models and clinical trials have presented promising results in this area, and warrant further investigations examining the effect of exercise on P-DPN.

Two-dimensional hydrodynamic simulations are performed to investigate explosive nucleosynthesis in a collapsar using the model of MacFadyen and Woosley (1999). It is shown that 56Ni is not produced in the jet of the collapsar sufficiently to explain the observed amount of a hypernova when the duration of the explosion is \\sim 10 sec, which is considered to be the typical timescale of explosion in the collapsar model. Even though a considerable amount of 56Ni is synthesized if all explosion energy is deposited initially, the opening angles of the jets become too wide to realize highly relativistic outflows and gamma-ray bursts in such a case. From these results, it is concluded that the origin of 56Ni in hypernovae associated with GRBs is not the explosive nucleosynthesis in the jet. We consider that the idea that the origin is the explosive nucleosynthesis in the accretion disk is more promising. We also show that the explosion becomes bi-polar naturally due to the effect of the deformed progenitor. This fact suggests that the 56Ni synthesized in the accretion disk and conveyed as outflows are blown along to the rotation axis, which will explain the line features of SN 1998bw and double peaked line features of SN 2003jd. Some fraction of the gamma-ray lines from 56Ni decays in the jet will appear without losing their energies because the jet becomes optically thin before a considerable amount of 56Ni decays as long as the jet is a relativistic flow. We show that abundance of nuclei whose mass number \\sim 40 in the ejecta depends sensitively on the energy deposition rate. So it may be determined by observations of chemical composition in metal poor stars which model is the proper one as a model of a gamma-ray burst accompanied by a hypernova.

Hereditary sensory and autonomic neuropathy (HASN) refers to a group of rare congenital disorders characterized by loss of pain sensation and other sensory or autonomic abnormalities. Among them, a relatively large proportion of patients with HSAN type IV, which is accompanied by anhidrosis and intellectual disability, are reported from Israel and Japan. HSAN type V, with normal sweating and mental development, is rarely reported in Japan. In 2009, we founded a research group for congenital insensitivity to pain and performed the first epidemiological survey of HSAN types IV and V in Japan. Questionnaires were sent to a total of 3,488 certified training institutions of five nationwide medical societies comprising pediatricians, neurologists, orthopedic surgeons, and dentists. Answers were obtained from 1,610 institutions, and 192 HSAN patients (152 with type IV and 28 with type V) were reported from 105 institutions. After excluding duplicated patients, we identified a total of 62 current, 36 past, and five deceased patients for HSAN-IV, and a total of 14 current, 13 past, and 0 deceased patients for HSAN-V. Using these figures, we estimated that the number of Japanese patients with HSAN types IV and V as 130-210 and 30-60 patients, respectively. We identified no gender differences, and patients with a family history of the disorder were limited to affected siblings in both conditions. Most patients with HSAN-IV were 5-40 years of age, whereas half of the patients with HSAN-V were 40 years or older. PMID:23495212

Hereditary neuropathies represent approximately 40% of undiagnosed neuropathies in a tertiary clinic setting. The Charcot-Marie-Tooth neuropathies (CMT) are the most common. Mutations in more than 40 genes have been identified to date in CMT. Approximately 50% of CMT cases are accounted for by CMT type 1A, due to a duplication within the peripheral myelin protein 22 gene (PMP22). Mutations in the gap junction beta 1 gene (GJB1), the myelin protein zero gene (MPZ), and the mitofusin 2 gene (MFN2) account for a substantial proportion of other genetically definable CMT. Some 15% of demyelinating CMT and 70% of axonal CMT await genetic clarification. Other hereditary neuropathies include the hereditary sensory and autonomic neuropathies, the familial amyloid polyneuropathies, and multisystem disorders (e.g., lipid storage diseases and inherited ataxias) that have peripheral neuropathy as a major or minor component. This review surveys the challenges of developing effective therapies for hereditary neuropathies in terms of past, present, and future experimental therapeutics in CMT. PMID:19019301

Objective: Paraneoplastic neuropathy is a clinical and immunological heterogeneous disorder and attempts have been made to classify subgroups of this disease. Only 30–50% of the clinical defined cases have antineuronal antibodies. Methods: The clinical and immunological features of 36 patients with paraneoplastic neuropathy from the authors' database were analysed including the type and course of the neuropathy, associated tumours, and the presence of antineuronal and other autoantibodies. Results: Antineuronal antibodies were detected in 17/36 patients (47%) and anti-Hu was the most frequent antineuronal antibody. Nine patients had high titre antinuclear antibodies (ANA, median titre 1/1000) without antineuronal antibodies. ANA reactivities were different in most patients. Comparison of the ANA positive and ANA negative patients revealed that ANA positive paraneoplastic neuropathy is more frequently associated with breast cancer but is not associated with lung cancer (p<0.05). The main clinical type in these patients was sensorimotor neuropathy. No ANA positive patient had central nervous system involvement. Although the Rankin score at the time of diagnosis was not different, the functional outcome in ANA positive patients was better than in ANA negative patients (p<0.05). Conclusions: Paraneoplastic neuropathy is a heterogeneous disorder. ANA may define a subgroup of paraneoplastic neuropathy with different clinical and immunological features and may be related to better prognosis of the neuropathic symptoms. PMID:16291897

OBJECTIVE To explore the relationship between serum neuron-specific enolase (NSE) levels and diabetic neuropathy. RESEARCH DESIGN AND METHODS Type 1 or 2 diabetic and healthy control subjects (n = 568) were randomly enrolled in a cross-sectional study. Diabetic neuropathy status was documented by the presence of clinical symptoms or signs, electromyography, quantitative sensory tests, and cardiac autonomic neuropathy tests. The severity of the neuropathy was staged by composite scores. Serum NSE was measured using electrochemiluminescence immunoassay. The demographic and clinical variables were obtained through an interviewer questionnaire. RESULTS Serum NSE levels increased slightly in diabetic subjects compared with normal subjects (9.1 [1.5] vs. 8.7 [1.7], P = 0.037), and the levels increased greatly in diabetic subjects with neuropathy compared with those without (10.8 [2.8] vs. 9.1 [1.5], P = 0.000). The association of NSE with diabetic neuropathy was independent of the hyperglycemic state (fasting blood glucose, HbA1c, duration, and the type of diabetes) and other potential confounders affecting NSE levels (e.g., age, sex, and renal status) (odds ratio 1.48 [1.13–1.74], P = 0.001). In addition, NSE levels increased with and were closely correlated to the stages of neuropathy (r = 0.63 [0.52–0.74], P = 0.000). The optimal cutoff point for serum NSE levels to distinguish patients with diabetic neuropathy from those without was 10.10 ?g/L, with a sensitivity of 66.3% and a specificity of 72.5%. CONCLUSIONS Serum NSE levels are closely associated with peripheral neuropathy in patients with diabetes. Future studies are warranted to clarify the relationship. PMID:23846809

Suprascapular neuropathy is generally considered to be a diagnosis of exclusion, although it has been described in association with several activities and conditions. To our knowledge, this is the first description of suprascapular neuropathy with complete neurogenic fatty replacement in patients with intact rotator cuff tendons in the absence of traction or compression mechanisms. We present 4 cases of patients who presented with complete fatty infiltration of the supraspinatus (1 patient), infraspinatus (2 patients), and both (1 patient) resulting from suprascapular neuropathy. Each of these patients underwent arthroscopic suprascapular nerve decompression and subsequently had immediate improvement in pain and subjective shoulder value. PMID:24630957

Peripheral neuropathy (PN) is one of the most common side effects of bortezomib therapy. The majority of bortezomib-related PN is a sensory neuropathy of mild to moderate degree, and is reversible after dose reduction or discontinuation. However, occasionally bortezomib-induced neuropathy can be severe and affects motor and/or autonomic nerves, and may be mediated by immune process. The role of immune modulation therapy in the management of bortezomib-induced PN was not well established. Here, we reported a case of bortezomib-induced severe PN that responded well to plasma exchange and steroid treatment. PMID:23211009

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An occurrence of peripheral neuropathy in nine 14- to 55-day-old racing pigeons was documented. The predominant clinical signs were diarrhea, and leg and wing paralysis. Grossly, there was discoloration and swelling of all the peripheral nerve trunks. Microscopic lesions comprising swelling, fragmentation and demyelination of myelin sheaths, and proliferation of Schwann cells, were seen in the peripheral nerves of all birds examined. These changes were associated with moderate to severe swelling, fragmentation, atrophy and loss of axons. The peripheral nerve lesions in these cases were similar to those of dietary riboflavin deficiency in chickens. An analysis of the diet given to the pigeons indicated that the riboflavin concentration was only 0.9 mg/kg feed. PMID:8672588

With the prevalence of diabetes mellitus (DM) increasing, pathologic complications such as diabetic peripheral neuropathy (DPN) are also becoming more common. Of those diagnosed with DM, 10% to 20% of patients suffer from painful DPN. Until recently, only pregabalin and duloxetine possessed Food and Drug Administration (FDA) approval for this condition. However, FDA recently approved tapentadol-ER [extended release] (Nucynta ER) for painful DPN. Tapentadol-ER is an opioid analgesic commonly used for the treatment of moderate-to-severe chronic pain that contains a unique dual mechanism acting as both a weak mu-opiod receptor agonist and norepinephine-reuptake inhibitor. It is by way of this unique dual mechanism that allows for effective analgesic effects with increased tolerability. This new FDA approval provides an additional therapeutic option to treat DPN in symptomatic patients. PMID:24129223

The common peroneal nerve (CPN), a major terminal branch of the sciatic nerve, can be subject to a variety of pathologies, which may affect the nerve at any level from the lumbar plexus to its distal branches. Although the diagnosis of peripheral neuropathy is traditionally based on a patient's clinical findings and electrodiagnostic tests, magnetic resonance neurography (MRN) is gaining an increasing role in the definition of the type, site, and extent of peripheral nerve disorders. Current high-field MR scanners enable high-resolution and excellent soft-tissue contrast imaging of peripheral nerves. In the lower extremities, MR neurography has been employed in the demonstration of the anatomy and pathology of the CPN, as well as in the detection of associated secondary muscle denervation changes. This article reviews the normal appearance of the CPN as well as typical pathologies and abnormal findings at 3.0-T MR neurography of the lower extremity. PMID:21416383

Light and electron microscopic findings from two sural nerve biopsies obtained at a one-year interval from a patient with the clinical features of Seitelberger's disease are described. Ballooned axons with accumulations of membranous profiles, vesicles, mitochondria, and a homogeneous center were present, and there were masses of 90 A filaments in endothelial, endoneurial, perineurial, and Schwann cells. These pathological alterations were less prominent in the second nerve biopsy, which showed a more pronounced decrease in myelinated fibers. The case shows that a generalized increase of 90 A filaments in structures of the peripheral nervous system is not a phenomenon exclusively occurring in patients with giant axonal neuropathy and, furthermore, that it may be a transitory feature. PMID:575280

Neuropathy target esterase (NTE) was shown to be an excellent biochemical marker for screening of organophosphates (OPs) with respect to their ability to result in organophosphate induced delayed neurotoxicity (OPIDN). This paper describes a new biosensor approach to the analysis of NTE and its inhibitors. The method is based on the combination of NTE enzymatic hydrolysis of phenyl valerate (PV) with phenol detection by the Clark-type oxygen electrode modified by immobilized tyrosinase. The validity of this biosensor method is confirmed by the facts that the calibration curves for NTE obtained by colorimetric and flow-through electrochemical methods were nearly identical and the titration of NTE by test inhibitor mipafox was shown to yield the same pI50 values. The developed electrochemical methods can be considered as a promising approach both for serial express NTE analysis and for kinetic characteristics of NTE. PMID:10421495

Sarcoidosis is a chronic inflammatory illness and small-fiber neuropathy (SFN) is one of the disabling and often chronic manifestations of the disease. SFN presents with peripheral pain and symptoms of autonomic dysfunction. The character of the pain can be burning or shooting. Besides, allodynia and hyperesthesia can exist. Diagnosis is usually made on the basis of clinical features, in combination with abnormal specialized tests. The aim of treatment is often to reduce pain; however, total pain relieve is seldom achieved. The role of TNF-? in the pathogenesis of SFN in sarcoidosis appears interesting to explore. Novel therapeutic agents such as ARA 290, a nonhematopoietic erythropoietin analogue with potent anti-inflammatory and tissue protective properties, are interesting to explore in the treatment of SFN in sarcoidosis. PMID:23304492

Background Diabetic peripheral neuropathy (DPN) accounts for 80% of diabetic foot ulceration; therefore neurologic examination plays a critical role in screening at risk patients. Our objective was assessment the prevalence of DPN and related factors based on clinical findings. Methods: This cross-sectional study was conducted on 124 diabetics who were randomly recruited from Diabetes Clinic of Dr. Shariati University Hospital (Tehran/Iran) in 2004. After gathering demographic data and blood sampling for fasting blood sugar (FBS), the questionnaires United Kingdom (UK), Michigan, Diabetic Neuropathy Score (DNS), and 10-g monofilament testing were administered. Analysis tests were chi-square, pearson correlation and logistic regression. Results: The patient’s age ranged 17–75 years; with 44% male. Ninety one percent suffered from type two diabetes and the mean duration of diabetes was 10 years. The mean FBS level was 181.5 mg/dl. While the prevalence of DPN based on Michigan, DNS, and monofilament testing was about 32–38%, some 54% were diagnosed by UK test. Tingling in the lower extremity was the most frequent complaint (42%). The strongest linear correlation was reported between Michigan and DNS (r= 0.7), and then between monofilament test and DNS (r= 0.6). The age > 50 years, length of diabetes > 10 years, and FBS >200 mg/dl were the main risk factors for DPN based on DNS. Conclusion: It seems that the combination of Michigan and monofilament test can provide an accurate screening tool for detecting DPN. In addition, tight glucose control, regular assessment of the lower extremity, and to educate diabetics is urged in elderly diabetics, longer duration of diabetes, and those with high FBS. PMID:23113086

The term 'laryngeal neuropathy' (LN) has first been used in veterinary medicine to describe an idiopathic and typically exercise induced inspiratory noise in horses.Nowadays, the term is often used in relation with intermittent vocal cord pareses in humans. Some authors use the term 'irritable larynx syndrome' (ILS) in a similar context. This article reviews the state of knowledge regarding LN and ILS and discusses the somewhat confusing terminology.For this systematic review a selective literature research in PubMed has been carried out.35 articles were found, which report on LN in animals and 17 articles reported on humans. 4 of these articles used the term 'irritable larynx syndrome'.Laryngeal neuropathy in horses usually affects the left recurrent laryngeal nerve and results in decreased vocal cord abduction and an inspiratory roaring or whistling noise, particularly during exercise. In dogs LN has been reported to also occur bilaterally. In association with humans LN has not been defined clearly in the literature. The term ILS on the other hand has only been used in relation to humans. The term describes a hypersensitivity of the laryngeal structures towards external stimuli, which causes symptoms such as dyspnea or cough among others. Sufficient knowledge does not exist for either of the 2 diseases, ILS or LN. As of yet, the term LN should not be used in human medicine to describe according symptoms of unknown aetiology. The term 'laryngeal movement disorder' seems a lot more appropriate. The symptom oriented term irritable larynx syndrome also seems suitable to describe laryngeal hypersensitivity appropriately. PMID:22638931

Immune-mediated neuropathies associated with non-Hodgkin's lymphoma are rare and can be difficult to delineate from neuropathies of other etiologies. We report the clinical and pathological findings of a 36-year-old patient with fulminant quadriplegic neuropathy, left facial nerve palsy, and Burkitt-like lymphoma. Features of the neuropathy, which occurred during induction chemotherapy with a total cumulative dose of 4 mg vincristine, suggested axonal Guillain-Barré syndrome. There was no evidence of direct malignant infiltration of the peripheral nervous system. We hypothesize that immune mechanisms triggered by the lymphoma initiated damage to the peripheral nervous system and enhanced its vulnerability to the toxic effects of vincristine. PMID:16671108

Chronic metformin use results in vitamin B12 deficiency in 30% of patients. Exhaustion of vitamin B12 stores usually occurs after twelve to fifteen years of absolute vitamin B12 deficiency. Metformin has been available in the United States for approximately fifteen years. Vitamin B12 deficiency, which may present without anemia and as a peripheral neuropathy, is often misdiagnosed as diabetic neuropathy, although the clinical findings are usually different. Failure to diagnose the cause of the neuropathy will result in progression of central and/or peripheral neuronal damage which can be arrested but not reversed with vitamin B12 replacement. To my knowledge, this is the first report of metformin-induced vitamin B12 deficiency causing neuropathy. PMID:20134380

As of 2010, diabetes affected nearly 25.8 million people in the United States, an increase of 25% from 2005. Nearly half of these individuals experience diabetic peripheral neuropathy (DPN), a serious complication of ...

Pyridoxine deficiency and excess have been implicated as a cause for peripheral neuropathy. As a result, unrelated neuropathies are often treated with pyridoxine based on questionable evidence. However, neurological practitioners frequently discourage patients from taking pyridoxine in excess of 50 mg/d given concerns around the development of a toxic sensory neuronopathy. There is no systematic review to support either of the 2 practices. To address this gap in knowledge, we reviewed the available literature on neuropathy attributed to pyridoxine deficiency and excess. Based on the current limited data, it can be concluded that very low doses of daily pyridoxine are required to prevent peripheral neuropathy. There is inadequate evidence to support routine pyridoxine supplementation in patients with disorders of peripheral nervous system. Supplementation with pyridoxine at doses greater than 50 mg/d for extended duration may be harmful and should be discouraged. PMID:25137514

Introduction: Mononeuropathies, in general, are very uncommon in childhood. Sciatic neuropathy (SN) is probably underappreciated in childhood and likely to represent nearly one quarter of childhood mononeuropathies. Materials and Methods: We present a 7-year-old girl who presented with painful right lower limb and abnormal gait. Detailed investigation revealed transient eosinophilia, abnormal neurophysiology, and magnetic resonance imaging (MRI) suggestive of isolated sciatic neuropathy. Results: She has responded very well to physiotherapy and has made a complete motor recovery, although she is left with an area of abnormal sensation affecting the lateral border of her right leg and the dorsum of her foot. Discussion: Differential diagnoses for pediatric SN have been discussed including compressive neuropathies in children and various hyper-eosinophilia syndromes. Compressive neuropathies in childhood are very rare and compression of the sciatic nerve is the second most common group after peroneal nerve lesion. PMID:24082941

The infantile-onset axonal neuropathies and neuronopathies are an uncommon and heterogeneous group of conditions causing weakness, wasting, and developmental delay in early childhood. Many are associated with central nervous system or other systemic manifestations and cause early mortality. We review the axonal Charcot-Marie-Tooth subtypes with onset in infancy, spinal muscular atrophy, and related syndromes of early infancy, giant axonal neuropathy, infantile neuroaxonal dystrophy, hereditary motor and sensory neuropathy with agenesis of the corpus callosum, early-onset neuropathies associated with mitochondrial disorders, and other less well-delineated clinical entities. Useful clinical and neuropathologic features in the diagnostic work-up of these conditions are also presented. PMID:22971091

Natura non facit saltus (Latin for "nature does not make jumps") is a maxim expressing the idea that natural things and properties change gradually, in a continuum, rather than suddenly. In biomedical sciences, for taxonomic purposes, we make jumps that emphasize differences more than similarities. Among the dysimmune neuropathies, 2 disorders, characterized by the presence of antibodies to gangliosides GM1 and GD1a and a peculiar, exclusive motor involvement, have been identified: acute motor axonal neuropathy (AMAN) and multifocal motor neuropathy (MMN). However, anti-GM1 or -GD1a antibodies are also associated with acute motor and sensory axonal motor neuropathy (AMSAN). We review the results of recent clinical and experimental studies showing that AMAN and MMN are not exclusively motor. We discuss the possible explanations for the greater resistance of sensory fibers to antibody attack to finally suggest that AMAN, AMSAN, and MMN belong to a continuous spectrum with a common pathophysiological mechanism. PMID:23625341